Sites of Tau Important for Aggregation Populate β-Structure and Bind to Microtubules and Polyanions

Name: Work Video:
Duration: 3 min 30 s
Marco D. Mukrasch; Jacek Biernat; Martin von Bergen�; Christian Griesinger; Eckhard Mandelkow�; Markus Zweckstetter
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'aggregation': [1, 176, 480, 494, 611, 952, 975, 1232, 2807, 3614, 3707], 'of': [2, 9, 14, 17, 26, 38, 51, 55, 75, 89, 92, 122, 133, 141, 146, 177, 184, 189, 192, 201, 213, 226, 230, 250, 264, 267, 297, 308, 316, 321, 372, 393, 465, 531, 649, 688, 832, 844, 859, 958, 976, 1084, 1091, 1120, 1172, 1176, 1215, 1220, 1233, 1254, 1272, 1313, 1355, 1359, 1452, 1515, 1557, 1609, 1663, 1675, 1697, 1713, 1812, 1904, 1956, 2001, 2169, 2232, 2242, 2273, 2280, 2348, 2353, 2360, 2367, 2386, 2401, 2405, 2408, 2428, 2535, 2590, 2592, 2601, 2618, 2637, 2666, 2675, 2739, 2749, 2771, 2782, 2808, 2834, 2846, 2861, 2871, 2885, 2892, 2901, 2904, 2927, 2939, 2949, 2959, 2962, 2966, 3002, 3023, 3039, 3054, 3074, 3080, 3083, 3090, 3164, 3167, 3181, 3237, 3240, 3251, 3277, 3293, 3331, 3346, 3350, 3353, 3362, 3368, 3373, 3394, 3412, 3437, 3445, 3448, 3466, 3478, 3485, 3502, 3516, 3532, 3539, 3557, 3631, 3678, 3683, 3706, 3713, 3721, 3749, 3760, 3820, 3847, 3852, 3871, 3902, 3921, 3939, 3947, 3951, 4025, 4045, 4054, 4069, 4072, 4081, 4091, 4105, 4108, 4122, 4141, 4148, 4157, 4190, 4199, 4202, 4207, 4225, 4236, 4262, 4292, 4297, 4307, 4312, 4405, 4417, 4443, 4451, 4486, 4493, 4517, 4521, 4535, 4543, 4563, 4596], 'the': [3, 15, 23, 35, 48, 52, 73, 87, 90, 120, 123, 127, 131, 144, 151, 163, 178, 190, 198, 210, 223, 227, 248, 262, 265, 295, 298, 302, 306, 319, 326, 338, 359, 373, 394, 460, 466, 475, 478, 489, 504, 528, 532, 535, 577, 602, 672, 686, 826, 830, 841, 845, 853, 857, 956, 959, 974, 1082, 1088, 1092, 1118, 1169, 1173, 1196, 1212, 1225, 1243, 1267, 1314, 1328, 1356, 1360, 1371, 1380, 1408, 1508, 1661, 1680, 1810, 1825, 1828, 1834, 1840, 1901, 1913, 1916, 1942, 1950, 1958, 1966, 1999, 2004, 2176, 2188, 2220, 2223, 2243, 2349, 2358, 2361, 2398, 2406, 2429, 2459, 2531, 2551, 2575, 2587, 2593, 2597, 2619, 2629, 2638, 2737, 2766, 2780, 2794, 2805, 2859, 2869, 2872, 2883, 2902, 2911, 2922, 2937, 2944, 2947, 2951, 2960, 2970, 2993, 3003, 3024, 3034, 3037, 3071, 3081, 3094, 3103, 3130, 3143, 3151, 3165, 3182, 3223, 3234, 3238, 3249, 3274, 3278, 3283, 3329, 3332, 3338, 3343, 3347, 3374, 3395, 3413, 3423, 3427, 3446, 3457, 3464, 3468, 3471, 3475, 3483, 3486, 3500, 3523, 3549, 3554, 3573, 3578, 3602, 3606, 3624, 3629, 3642, 3647, 3676, 3679, 3699, 3704, 3719, 3732, 3765, 3781, 3784, 3806, 3823, 3850, 3862, 3869, 3881, 3891, 3908, 3911, 3927, 3945, 3967, 3985, 3998, 4010, 4030, 4043, 4046, 4062, 4070, 4073, 4076, 4084, 4109, 4113, 4134, 4138, 4166, 4197, 4213, 4223, 4226, 4234, 4255, 4258, 4269, 4272, 4290, 4295, 4305, 4309, 4362, 4367, 4397, 4411, 4420, 4435, 4440, 4444, 4491, 4494, 4507, 4532, 4550, 4561, 4593, 4597, 4614, 4636], 'microtubule-associated': [4, 179, 510], 'tau': [5, 30, 57, 115, 180, 205, 232, 290, 419, 505, 633, 675, 751, 785, 977, 1059, 1200, 1217, 1234, 1262, 1316, 1334, 1372, 2244, 2354, 2809, 3613, 4237, 4308], 'protein': [6, 181, 356, 420, 511, 533, 846, 1361, 1386, 1414, 1592, 2014, 3807, 3892, 4031, 4077, 4085, 4110], 'and': [7, 34, 125, 136, 148, 182, 209, 300, 311, 323, 481, 518, 534, 652, 683, 758, 829, 896, 961, 965, 986, 1114, 1198, 1203, 1237, 1247, 1258, 1362, 1376, 1399, 1407, 1428, 1495, 1542, 1634, 1715, 1752, 1770, 1797, 1814, 1833, 1878, 1912, 1996, 2020, 2026, 2031, 2052, 2095, 2109, 2121, 2126, 2134, 2146, 2152, 2161, 2172, 2179, 2184, 2200, 2217, 2225, 2234, 2249, 2260, 2267, 2283, 2290, 2351, 2390, 2412, 2432, 2466, 2505, 2537, 2569, 2614, 2646, 2655, 2668, 2681, 2700, 2732, 2761, 2786, 2792, 2798, 2850, 2879, 3006, 3021, 3030, 3044, 3049, 3109, 3134, 3205, 3215, 3225, 3285, 3300, 3355, 3357, 3377, 3398, 3402, 3505, 3512, 3518, 3567, 3581, 3620, 3628, 3691, 3725, 3731, 3744, 3755, 3772, 3792, 3961, 3981, 4078, 4150, 4159, 4192, 4218, 4245, 4302, 4366, 4369, 4378, 4385, 4447, 4454, 4565, 4572, 4620], 'formation': [8, 160, 183, 335, 2074, 2156], '"neurofibrillary': [10, 185], 'tangles"': [11, 186], 'is': [12, 187, 352, 472, 501, 508, 569, 680, 748, 1060, 1324, 1938, 2377, 2583, 2856, 2888, 2977, 2987, 3068, 3154, 3271, 3289, 3319, 3527, 3559, 3565, 3664, 4274, 4393], 'one': [13, 188, 464, 1943, 2636, 3946, 4279], 'hallmarks': [16, 191], 'Alzheimer': [18, 193, 350, 470, 790], 'disease.': [19, 194], 'mechanisms': [21, 37, 196, 212], 'underlying': [22, 197], 'structural': [24, 199, 490, 760, 1164, 2997], 'transition': [25, 200], 'innocuous,': [27, 202], 'natively': [28, 203, 689], 'unfolded': [29, 204, 690, 1089, 2284, 2682], 'to': [31, 40, 81, 85, 206, 215, 256, 260, 445, 448, 473, 482, 485, 542, 685, 972, 1163, 1195, 1227, 1332, 1694, 1805, 1910, 1941, 2610, 2635, 2765, 2801, 2895, 2936, 3322, 3400, 3426, 3525, 3572, 3615, 3667, 3742, 3769, 3789, 3877, 3944, 3977, 3997, 4033, 4075, 4088, 4097, 4133, 4152, 4161, 4289, 4409, 4526, 4530, 4588, 4613, 4629], 'neurotoxic': [32, 207], 'forms': [33, 208, 856], 'detailed': [36, 211], 'binding': [39, 145, 214, 320, 547, 2206, 3378, 3393, 3424, 3524, 3551, 4071, 4156, 4412, 4449, 4583], 'microtubules': [41, 112, 149, 155, 216, 287, 324, 330], 'are': [42, 168, 217, 343, 443, 495, 540, 787, 967, 970, 1184, 1907, 2219, 2436, 2671, 3017, 3096, 3142, 3171, 3217, 3302, 3610, 4456, 4539, 4602], 'largely': [43, 218, 3924, 4125], 'unknown.': [44, 219], 'Here': [45, 220, 1166], 'we': [46, 221, 1167, 1238, 3709], 'report': [47, 222, 1168], 'high-resolution': [49, 224, 1074, 1170, 2483], 'characterization': [50, 225, 1171], 'repeat': [53, 228, 838, 854, 1174, 1188, 1213, 2245, 2983, 3075, 3188, 3287, 3334, 3348, 3488, 3563, 3608, 4580, 4598], 'domain': [54, 229, 1175, 1214, 2246, 3349], 'soluble': [56, 231, 1216, 1502], 'using': [58, 233, 1772, 2209, 2380, 2550, 4165], 'multidimensional': [59, 234, 2381], 'NMR': [60, 62, 235, 237, 1157, 1584, 1738, 1755, 1766, 2142, 2362, 2382, 2402, 2446, 2529, 3458, 4167, 4214, 4270, 4445, 4533], 'spectroscopy.': [61, 236], 'secondary': [63, 238, 696, 1961, 1969, 2411, 2676, 2752, 2837, 2863, 2913, 3008, 3057, 3111, 3178, 3227, 3313], 'chemical': [64, 239, 1831, 1902, 2194, 2202, 2227, 2274, 2603, 2648, 2662, 2753, 2838, 2864, 2914, 2933, 3009, 3112, 3179, 3228, 3314, 3414, 3434, 3452, 3494, 3540, 3595, 3625, 3824, 3858, 3912, 3993, 4064, 4114, 4168, 4483, 4639], 'shifts': [65, 240, 1832, 1903, 1962, 2203, 2649, 2719, 2754, 2839, 2865, 2915, 2934, 3010, 3113, 3180, 3229], 'detect': [66, 241], 'residual': [67, 242, 1221, 3256], 'β-structure': [68, 243, 1222, 2773, 2897, 3061, 3066, 3095, 3169, 3242, 3257, 3269, 3340], 'for': [69, 170, 244, 345, 477, 503, 765, 1072, 1231, 1498, 1670, 1684, 1706, 1722, 1809, 1839, 1875, 1972, 2083, 2164, 2197, 2729, 2757, 2804, 2842, 2979, 3026, 3093, 3317, 3417, 3553, 3600, 3612, 3658, 3736, 3777, 3813, 3836, 4093, 4276, 4429, 4585, 4644], '8–10': [70, 245, 3246], 'residues': [71, 246, 775, 1240, 1906, 2002, 2758, 2928, 2965, 3027, 3042, 3247, 3439, 3469, 3520, 3583, 3604, 3838, 3854, 4488], 'at': [72, 130, 247, 305, 574, 955, 1070, 1636, 1667, 1687, 1735, 1743, 1845, 2037, 2159, 2257, 2586, 2779, 2868, 3233, 3248, 3273, 3482, 3634, 3675, 3739, 3762, 3774, 3810, 3866, 3932, 3964, 4003, 4036, 4100, 4216, 4229, 4252, 4281, 4387, 4500, 4512, 4605, 4625], 'beginning': [74, 132, 249, 307, 957, 2781, 2870, 3038, 3250, 3484], 'repeats': [76, 124, 134, 251, 299, 309, 526, 578, 963, 1183, 1312, 2783, 2875, 2994, 3047, 3252], 'R2–R4.': [77, 252], 'These': [78, 253, 441, 969, 2718, 2776, 3296, 4058, 4431], 'regions': [79, 254, 1219, 3035, 3089, 3166, 3212, 3239, 3260], 'correspond': [80, 255], 'sequence': [82, 257, 2439, 2579, 3200], 'motifs': [83, 129, 258, 304, 992, 2440, 2624, 2791, 2796, 3146, 3208], 'known': [84, 259, 496, 502, 541, 2800], 'form': [86, 261, 1083, 2896], 'core': [88, 263, 858], 'cross-β-structure': [91, 266, 985, 1119], 'tau-paired': [93, 268], 'helical': [94, 106, 158, 172, 269, 281, 333, 347, 405, 639, 982, 3122], 'filaments.': [95, 270], 'Chemical': [96, 271], 'shift': [97, 272, 1820, 1970, 2195, 2604, 3415, 3435, 3453, 3495, 3541, 3596, 3626, 3825, 3859, 3913, 3994, 4065, 4115, 4169, 4484, 4640], 'perturbation': [98, 273, 4170], 'studies': [99, 274, 1917], 'show': [100, 275, 1210, 2720, 2931, 3051, 3106, 3254, 4433], 'that': [101, 153, 276, 328, 512, 782, 1211, 1223, 1250, 1973, 2441, 2858, 2924, 2992, 3014, 3064, 3132, 3199, 3323, 3328, 3522, 3548, 3609, 3674, 3805, 3827, 3893, 3915, 4052, 4061, 4434, 4448, 4578], 'polyanions,': [102, 277], 'which': [103, 167, 278, 342, 1179, 2582, 3718, 4117, 4185], 'promote': [104, 279, 1251], 'paired': [105, 157, 171, 280, 332, 346, 404, 638, 981], 'filament': [107, 159, 173, 282, 334, 348], 'aggregation,': [108, 283, 3669, 4128], 'as': [109, 111, 284, 286, 362, 770, 1159, 1229, 1281, 1615, 1824, 1900, 3203, 3584, 3687], 'well': [110, 285, 2409], 'interact': [113, 288], 'with': [114, 289, 692, 984, 1245, 1248, 1374, 1394, 1426, 1481, 1490, 1604, 1710, 1718, 2011, 2098, 2112, 2124, 2137, 2253, 2288, 2355, 2370, 2502, 2921, 2956, 3129, 3261, 3307, 3534, 3575, 3623, 3652, 3756, 3849, 3880, 3935, 3984, 4020, 4238, 4383, 4460, 4592], 'through': [116, 126, 291, 301], 'positive': [117, 292, 3107, 3176], 'charges': [118, 293], 'near': [119, 294, 825], 'ends': [121, 296, 3163], 'β-forming': [128, 303], '2': [135, 310, 1533, 1575, 3564, 3778, 3782, 3864, 3930, 4001], '3.': [137, 312, 1799], 'high': [139, 314, 2278, 3091, 3168, 3210, 3241, 3263, 3431, 3635, 4089, 4098, 4513], 'degree': [140, 315, 2279], 'similarity': [142, 317], 'between': [143, 318, 1827, 2222, 3259, 3723], 'polyanions': [147, 322, 654, 1249, 3396, 3526, 3558], 'supports': [150, 325], 'hypothesis': [152, 327], 'stable': [154, 329, 1378], 'prevent': [156, 331, 486], 'by': [161, 336, 354, 369, 451, 458, 571, 647, 653, 699, 822, 1352, 1363, 1440, 1506, 1553, 1918, 1965, 1998, 2077, 2397, 3099, 3175, 3406, 3442, 3639, 3689, 3841, 3919, 4120, 4211, 4242, 4373, 4490], 'blocking': [162, 337], 'tau-polyanion': [164, 339], 'interaction': [165, 340, 991, 1244, 3375, 3574], 'sites,': [166, 341], 'crucial': [169, 344], 'formation.': [174, 349], 'disease': [351], 'characterized': [353, 4164, 4241], 'abnormal': [355, 2806], 'deposits': [357], 'in': [358, 469, 497, 527, 545, 576, 754, 776, 789, 840, 901, 1081, 1178, 1242, 1266, 1276, 1389, 1436, 1445, 1459, 1593, 1642, 1660, 1729, 1915, 1953, 1976, 2003, 2065, 2175, 2187, 2238, 2286, 2438, 2542, 2628, 2652, 2664, 2679, 2917, 2943, 3036, 3046, 3070, 3114, 3127, 3138, 3147, 3157, 3187, 3213, 3219, 3282, 3298, 3304, 3324, 3342, 3474, 3499, 3585, 3605, 3646, 3698, 3717, 3816, 3830, 3890, 3954, 3971, 4143, 4184, 4196, 4294, 4321, 4396, 4414, 4419, 4457, 4555, 4560, 4608], 'brain,': [360], 'such': [361, 3202, 3804], 'amyloid': [363], 'plaques': [364], 'or': [365, 392, 457, 524, 702, 835, 1187, 1590, 3124, 3140, 4027, 4096, 4389, 4523, 4537], 'neurofibrillary': [366], 'tangles,': [367], 'formed': [368], 'fibrous': [370], 'assemblies': [371], 'Aβ': [374, 493], 'peptide': [375], '(1Selkoe': [376], 'D.J.': [377, 3381, 4173], 'Schenk': [378], 'D.': [379, 1037], 'Annu.': [380], 'Rev.': [381], 'Pharmacol.': [382], 'Toxicol.': [383], '2003;': [384], '43:': [385], '545-584Crossref': [386], 'PubMed': [387, 436, 562, 596, 627, 666, 723, 814, 891, 919, 945, 1019, 1053, 1111, 1148, 1300, 1629, 1792, 1867, 1895, 1931, 1990, 2310, 2339, 2496, 2522, 2564, 2695, 2713, 4351, 4477], 'Scopus': [388, 437, 563, 597, 628, 667, 815, 892, 920, 946, 1020, 1054, 1149, 1301, 1630, 1793, 1868, 1896, 1932, 1991, 2340, 2478, 2497, 2523, 2565, 2696, 2714, 4352, 4478], '(754)': [389], 'Google': [390, 439, 565, 599, 630, 669, 724, 817, 894, 922, 948, 1022, 1056, 1112, 1151, 1303, 1632, 1795, 1870, 1898, 1934, 1993, 2311, 2342, 2480, 2499, 2525, 2567, 2698, 2716, 3390, 4182, 4354, 4480], 'Scholar)': [391, 895, 1633, 1796, 1935, 2500, 2568, 4183], 'microtubule': [395], '(MT)': [396], '1The': [397], 'abbreviations': [398], 'used': [399, 1944], 'are:': [400], 'MT,': [401], 'microtubule;': [402], 'PHF,': [403], 'filament;': [406], 'MES,': [407, 1465, 1523, 1565], '4-morpholineethanesulfonic': [408], 'acid;': [409, 412], 'Pipes,': [410, 1648], '1,4-piperazinediethanesulfonic': [411], 'HSQC,': [413], 'heteronuclear': [414], 'single': [415], 'quantum': [416], 'correlation.': [417], '-associated': [418], '(2Mandelkow': [421], 'E.M.': [422, 555, 586, 622, 736, 910, 930, 1005, 1134, 1293, 1618, 2325, 2822, 4340, 4470], 'Mandelkow': [423, 554, 556, 585, 587, 619, 621, 660, 712, 735, 737, 909, 911, 929, 933, 1004, 1006, 1100, 1133, 1135, 1292, 1294, 2299, 2324, 2326, 2821, 2823, 4339, 4341, 4469, 4471], 'E.': [424, 557, 588, 620, 661, 709, 713, 738, 912, 934, 1007, 1097, 1101, 1136, 1295, 1381, 1409, 1442, 2296, 2300, 2327, 2824, 4342, 4472], 'Trends': [425], 'Cell': [426, 914], 'Biol.': [427, 715, 740, 810, 915, 1009, 1043, 1103, 1138, 1625, 2302, 2329, 2691, 2826, 3386, 4178, 4347], '1998;': [428, 942, 2692], '8:': [429], '425-427Abstract': [430], 'Full': [431, 433, 593, 720, 1014, 1016, 1048, 1050, 1108, 1143, 1145, 2307, 2334, 2336], 'Text': [432, 434, 594, 721, 1015, 1017, 1049, 1051, 1109, 1144, 1146, 2308, 2335, 2337], 'PDF': [435, 595, 722, 1018, 1052, 1110, 1147, 2309, 2338], '(445)': [438], 'Scholar).': [440, 566, 600, 631, 745, 818, 949, 1057, 1871, 2343, 2481, 2526, 2831, 3391, 4481], 'aggregates': [442], 'thought': [444], 'be': [446, 543, 645, 763, 2540, 2626, 2802, 2954], 'toxic': [447, 454], 'neurons,': [449], 'either': [450, 833, 1180, 3120], 'causing': [452], 'some': [453, 498, 3438, 3632], 'signaling': [455], 'defect': [456], 'obstructing': [459], 'cell': [461, 1455, 1494], 'interior.': [462], 'Therefore,': [463, 746, 2449], 'top': [467], 'priorities': [468], 'research': [471], 'understand': [474], 'reasons': [476], 'pathological': [479], 'find': [483], 'methods': [484], 'it.': [487], 'Although': [488], 'principles': [491, 761], 'governing': [492], 'detail,': [499], 'little': [500], 'protein.': [506], 'Tau': [507, 767, 1256, 2658, 4153], 'a': [509, 677, 755, 1061, 1073, 1390, 1482, 1491, 1554, 1695, 1730, 1977, 2270, 2277, 2346, 2371, 2843, 2893, 3052, 3060, 3084, 3121, 3125, 3231, 3255, 3262, 3291, 3443, 3536, 3711, 3757, 3936, 4101, 4319, 4359, 4582, 4630], 'regulates': [513], 'MT': [514, 546, 1643, 2165, 4381, 4514], 'stability,': [515], 'neurite': [516], 'outgrowth,': [517], 'other': [519, 673], 'MT-dependent': [520], 'functions.': [521], 'three': [523, 836, 2905, 2964, 3104], 'four': [525, 834, 1182, 1311, 2594, 3116], 'C-terminal': [529, 842, 2588, 2971, 3235], 'half': [530, 843], 'flanking': [536], 'proline-rich': [537], 'basic': [538], 'domains': [539], 'involved': [544, 1241], '(3Gustke': [548, 1286, 4463], 'N.': [549, 582, 805, 1287, 4464], 'Trinczek': [550, 1288, 4465], 'B.': [551, 1289, 4466], 'Biernat': [552, 614, 731, 907, 1002, 1131, 1290, 2322, 2817, 4467], 'J.': [553, 580, 615, 714, 732, 734, 808, 908, 913, 1003, 1008, 1042, 1102, 1132, 1137, 1291, 1623, 1783, 1786, 1855, 1860, 2301, 2323, 2328, 2489, 2516, 2558, 2818, 2820, 4345, 4468], 'Biochemistry.': [558, 623, 662, 1296, 4473], '1994;': [559, 717, 1105, 1297, 1892, 1928, 1987, 2304, 2710, 4474], '33:': [560, 1298, 4475], '9511-9522Crossref': [561, 1299, 4476], '(547)': [564, 1302, 4479], 'affinity': [568], 'regulated': [570], 'phosphorylation': [572, 604], 'particularly': [573, 1908, 3896], 'KXGS-motifs': [575], '(4Biernat': [579], 'Gustke': [581], 'Drewes': [583, 905], 'G.': [584, 906, 1781, 4332], 'Neuron.': [589], '1993;': [590, 2475], '11:': [591, 743, 2829], '153-163Abstract': [592], '(662)': [598], 'Interestingly': [601], 'same': [603, 3579, 3909, 4426, 4618], 'sites': [605], 'have': [606, 1154, 1224], 'an': [607, 771, 1160, 1545, 2450, 2543, 2940, 3793, 3899, 4518], 'inhibitory': [608], 'influence': [609, 4206], 'on': [610, 779, 1417, 1422, 1544, 1701, 1746, 2458, 2547, 2574, 3422, 3456], '(5Schneider': [612], 'A.': [613, 711, 803, 807, 880, 887, 941, 1001, 1099, 1130, 1785, 2298, 2321, 2469, 2488, 4344], 'von': [616, 926], 'Bergen': [617, 727, 927, 994, 1123, 2314, 2813], 'M.': [618, 728, 795, 864, 878, 928, 995, 1033, 1124, 1620, 2315, 2486, 2557, 2814], '1999;': [624], '38:': [625], '3549-3558Crossref': [626], '(460)': [629], 'Unbound': [632], 'can': [634, 644, 768, 3568], 'assemble': [635], 'into': [636, 978, 1235, 2810, 3197], 'Alzheimer-like': [637], 'filaments': [640, 983], '(PHFs)': [641], 'whose': [642], 'polymerization': [643, 1681], 'enhanced': [646], 'oxidation': [648], 'SH': [650], 'groups': [651], '(e.g.': [655], 'heparin,': [656, 3989, 4123], 'poly-Glu': [657, 2053, 3399], '(6Barghorn': [658], 'S.': [659, 801, 886, 940, 997, 1126, 1777, 1849, 2317, 2471], '2002;': [663, 811], '41:': [664], '14885-14896Crossref': [665], '(286)': [668], 'Scholar)).': [670, 1152, 2717], 'On': [671], 'hand,': [674], 'has': [676, 1066, 1190], 'hydrophilic': [678], 'character,': [679], 'highly': [681, 1062, 3942], 'soluble,': [682], 'belongs': [684], 'class': [687], 'proteins': [691, 1346, 1373, 1550, 2369, 2683], 'no': [693, 3065, 3888], 'apparent': [694], 'ordered': [695], 'structure': [697, 2350, 2414, 2677], 'detectable': [698], 'far-UV': [700], 'CD': [701, 2289], 'Fourier-transform': [703], 'infrared': [704], 'spectroscopy': [705, 1158], '(7Schweers': [706, 1094, 2293], 'O.': [707, 1095, 2294], 'Schonbrunn-Hanebeck': [708, 1096, 2295], 'Marx': [710, 1000, 1098, 1129, 2297, 2320], 'Chem.': [716, 1010, 1044, 1104, 1139, 1862, 2303, 2330, 2473, 2491], '269:': [718, 1106, 2305], '24290-24297Abstract': [719, 1107, 2306], 'Scholar,': [725, 923, 1023, 2312], '8von': [726], 'Friedhoff': [729, 2815], 'P.': [730, 797, 925, 932, 2816, 4336], 'Heberle': [733, 2819], 'Mol.': [739, 1624, 2825, 3385, 4177, 4346], 'Cell.': [741, 2827], '2000;': [742, 2828], '363AGoogle': [744, 2830], 'it': [747, 1065, 2606, 3288], 'unclear': [749], 'why': [750], 'should': [752], 'aggregate': [753, 769], 'specific': [756], 'manner': [757], 'what': [759], 'could': [762, 2539, 2625], 'responsible': [764], 'this.': [766], 'intact': [772], 'protein,': [773, 1064, 1093], '352–441': [774], 'length': [777], '(depending': [778], 'isoform),': [780], 'so': [781], 'all': [783, 1068, 1181, 1310, 2641, 3115, 3873], 'six': [784, 2746, 3603], 'isoforms': [786, 820, 1201], 'found': [788, 2756, 4394, 4558], 'PHFs': [791, 860, 2811, 3616], '(9Buee': [792], 'L.': [793, 999, 1027, 1128, 2319], 'Hamdane': [794], 'Delobel': [796], 'Sambo': [798], 'A.V.': [799], 'Begard': [800], 'Ghestem': [802], 'Sergeant': [804], 'Delacourte': [806], 'Soc.': [809, 1863, 2492], '196:': [812], '103-108Crossref': [813], '(7)': [816], 'differ': [821], 'two': [823, 953, 1189, 1513, 1711, 3555], 'inserts': [824], 'N-terminal': [827, 4612], 'end': [828, 2589, 3236, 3677, 4044], 'presence': [831, 1662, 2961, 3082, 4198, 4296, 4306], 'imperfect': [837], 'sequences': [839, 855, 3136], '(see': [847, 1205, 1305, 4324], 'Fig.': [848, 1206, 1306, 2853, 3831, 3955], '1).': [849, 1207, 1307], 'region': [851, 2919, 3073], 'comprising': [852], '(10Wischik': [861], 'C.M.': [862], 'Novak': [863], 'Thogersen': [865], 'H.C.': [866], 'Edwards': [867], 'P.C.': [868], 'Runswick': [869], 'M.J.': [870], 'Jakes': [871], 'R.': [872], 'Walker': [873], 'J.E.': [874], 'Milstein': [875], 'C.': [876], 'Roth': [877], 'Klug': [879], 'Proc.': [881, 935], 'Natl.': [882, 936], 'Acad.': [883, 937], 'Sci.': [884, 938], 'U.': [885, 939, 1622], '1988;': [888], '85:': [889], '4506-4510Crossref': [890], '(821)': [893], 'also': [897, 3155], 'promotes': [898], 'PHF': [899, 951], 'assembly': [900, 1644, 4251, 4382], 'vitro': [902], '(11Wille': [903], 'H.': [904, 1039, 4338], '1992;': [916], '118:': [917], '573-584Crossref': [918], '(436)': [921], '12Friedhoff': [924], 'Davies': [931], '95:': [943], '15712-15717Crossref': [944], '(295)': [947], 'For': [950, 2139, 4358], 'hexapeptides': [954], 'second': [960, 1329, 3284, 3333, 3487], 'third': [962, 3279, 3607], '(275VQI-INK280': [964], '306VQIVYK311)': [966], 'crucial.': [968], 'able': [971], 'initiate': [973], 'bona': [979], 'fide': [980], 'thereby': [987, 4136], 'represent': [988, 2995], 'minimal': [989, 1392, 1446], 'tau-tau': [990], '(13von': [993, 1122], 'Barghorn': [996, 1125, 2316], 'Li': [998, 1127, 2318], '2001;': [1011, 1140, 1864, 2331, 2493, 2519], '276:': [1012, 1141, 2332], '48165-48174Abstract': [1013, 1142, 2333], '(454)': [1021, 1150, 2341], '14Goux': [1024], 'W.J.': [1025], 'Kopplin': [1026], 'Nguyen': [1028], 'A.D.': [1029], 'Leak': [1030], 'K.': [1031], 'Rutkofsky': [1032], 'Shanmuganandam': [1034], 'V.D.': [1035], 'Sharma': [1036], 'Inouye': [1038], 'Kirschner': [1040], 'D.A.': [1041], '2004;': [1045, 2561, 4348], '279:': [1046], '26868-26875Abstract': [1047], '(190)': [1055], 'Because': [1058, 2600], 'flexible': [1063], 'resisted': [1067], 'attempts': [1069], 'crystallization': [1071], 'x-ray': [1075], 'structure.': [1076], 'X-ray': [1077], 'analyses': [1078], 'exist': [1079], 'only': [1080, 2269, 2418, 2608, 2963], 'solution': [1085], 'scattering': [1086], '(confirming': [1087, 1117], 'nature': [1090, 4595], 'Scholar))': [1113, 1304, 4355], 'fiber': [1115], 'diffraction': [1116], 'PHFs,': [1121, 1236], 'We': [1153], 'now': [1155], 'applied': [1156], 'alternative': [1161], 'approach': [1162], 'studies.': [1165], 'tau,': [1177, 1957], 'present': [1185, 3069, 3272], '(K18)': [1186], 'been': [1191], 'deleted': [1192], '(K19),': [1193], 'corresponding': [1194, 1331, 3072, 3428], 'adult': [1197], 'fetal': [1199, 1333], 'htau40': [1202], 'htau23': [1204], 'Our': [1208], 'findings': [1209], 'contains': [1218, 4581], 'potential': [1226], 'serve': [1228], 'seeds': [1230], 'identify': [1239], 'MTs': [1246, 4149, 4162, 4228, 4239, 4256, 4293, 4313, 4406, 4437], 'PHF-aggregation.': [1252], 'Expression': [1253], 'Recombinant': [1255], 'Constructs': [1257], 'Isotope': [1259], 'Labeling—': [1260], 'Human': [1261], 'constructs': [1263, 2247], 'were': [1264, 1347, 1438, 1457, 1488, 1551, 1692, 1727, 1741, 1768, 1803, 1822, 1880, 1963, 2008, 2070, 2207, 2255, 2265, 2508, 2650, 2755, 2840, 3440, 3480, 3497, 3587, 3598, 3828, 3839, 3875, 3916, 3923, 4006, 4067, 4118, 4124, 4194, 4240, 4364, 4371, 4407, 4503, 4557, 4623, 4642], 'expressed': [1265, 1345], 'vector': [1268], 'pNG2': [1269], '(a': [1270], 'derivative': [1271], 'pET-3a,': [1273], 'Merck-Novagen,': [1274], 'Darmstadt)': [1275], 'Escherichia': [1277], 'coli': [1278, 1382, 1410, 1443], 'strain': [1279], 'BL21(DE3)': [1280], 'described': [1282, 1616], '(Gustke': [1283], 'et': [1284, 1884, 1920, 2702, 4326], 'al.': [1285, 1885, 1921, 2703], 'K18': [1308, 1385, 1813, 2151, 2177, 2233, 2248, 2387, 2536, 2654, 2731, 3299, 3354, 3401, 3479, 3533, 3586, 3684, 3726, 3948, 4022, 4055, 4158, 4191, 4418, 4455, 4522, 4536, 4556, 4587], 'comprises': [1309], 'largest': [1315, 3472], 'isoform': [1317, 2768], '(residues': [1318, 1335, 2877], 'Gln244-Glu372': [1319], 'plus': [1320], 'initial': [1321, 3750], 'Met243),': [1322], 'K19': [1323, 1413, 1815, 2036, 2189, 2235, 2391, 2538, 2733, 2980, 3301, 3318, 3356, 3403, 4160, 4193, 4453, 4524, 4538], 'similar': [1325, 1940, 2844, 2975, 3537, 3694, 3943], 'but': [1326, 2631, 2722, 2898, 4284, 4317], 'lacks': [1327], 'repeat,': [1330, 3041, 3280, 4610], 'Met243': [1336], '+': [1337, 2213], 'Gln244-Lys274,': [1338], 'Val337-Glu372,': [1339], 'without': [1340, 3753, 3884, 3988, 4318], 'R2': [1341, 2984, 3048, 3214], '=': [1342, 2211], 'Val275-Ser305).': [1343], 'purified': [1348, 1614], 'from': [1349, 1882, 2071, 2725, 2789, 4233], 'bacterial': [1350], 'extracts': [1351], 'making': [1353], 'use': [1354], 'heat': [1357], 'stability': [1358, 4224], 'FPLC': [1364, 1546], 'SP-Sepharose': [1365, 1547], 'chromatography': [1366, 1518, 1560], '(Amersham': [1367], 'Biosciences).': [1368], 'To': [1369, 1948, 2344, 3702, 4221], 'label': [1370], '15N': [1375, 1429, 1437, 2201, 4013], '13C': [1377, 1400, 1427], 'isotopes,': [1379], 'culture': [1383, 1411], 'expressing': [1384, 1412], 'was': [1387, 1415, 1504, 1510, 1613, 1682, 2075, 2157, 2364, 2394, 2453, 2607, 3404, 3543, 3685, 3696, 3728, 3734, 3767, 3786, 3796, 3800, 3808, 3887, 3894, 3905, 3941, 4056, 4086, 4163, 4209, 4427], 'grown': [1388, 1416], 'M9': [1391], 'medium': [1393, 1420, 1447], '15NH4Cl': [1395], '(1': [1396], 'g': [1397, 1403, 1450], 'liter-1)': [1398, 1404], 'glucose': [1401], '(4': [1402], '(Campro': [1405], 'Scientific),': [1406], 'rich': [1418], 'growth': [1419], 'based': [1421, 2546], 'chemolithoautotrophic': [1423], 'bacteria': [1424, 1444], 'labeled': [1425, 2252], 'isotopes': [1430], '(Silantes).': [1431], 'Protein': [1432], 'samples': [1433, 1585, 2143, 4363], 'uniformly': [1434, 2012, 2149, 2251], 'enriched': [1435], 'prepared': [1439], 'growing': [1441], 'containing': [1448, 2015], '1': [1449, 1469, 1472, 1527, 1530, 1566, 1569, 1572, 1605, 1651, 1654, 1657, 1664, 1707], 'liter-1': [1451], '15NH4Cl.': [1453], 'pellets': [1456, 4370], 'resuspended': [1458], 'boiling': [1460], 'extraction': [1461], 'buffer': [1462, 1519, 1561, 1645], '(50': [1463], 'mm': [1464, 1467, 1470, 1473, 1476, 1522, 1525, 1528, 1531, 1534, 1537, 1564, 1570, 1573, 1576, 1579, 1588, 1599, 1606, 1647, 1652, 1655, 1658, 1665, 2017, 2022, 2028, 2033, 2148], '500': [1466], 'NaCl,': [1468, 1526, 1568], 'MgCl2,': [1471, 1532, 1574], 'EGTA,': [1474, 1529, 1571], '5': [1475, 1671, 1744, 2160, 2258, 3763, 3790, 4217, 4282, 4390, 4548], 'dithiothreitol,': [1477, 1535, 1577], 'pH': [1478, 1540, 1582, 1602, 1649, 1846, 1914, 2038, 2261], '6.8)': [1479, 1541], 'complemented': [1480], 'protease': [1483], 'inhibitor': [1484], 'mixture.': [1485], 'cells': [1487], 'disrupted': [1489], 'French': [1492], 'pressure': [1493], 'subsequently': [1496], 'boiled': [1497], '20': [1499, 1685, 2162, 4219, 4388, 4501, 4626, 4634], 'min.': [1500, 1672], 'extract': [1503], 'isolated': [1505], 'centrifugation,': [1507], 'supernatant': [1509], 'dialyzed': [1511], 'against': [1512], 'changes': [1514, 3416, 3436, 3496, 3542, 3597, 3627, 3826, 3914, 4066, 4485, 4641], 'cation': [1516, 1558], 'exchange': [1517, 1559, 3306, 3454], 'A': [1520, 2482, 2973, 2999, 3693, 4301], '(20': [1521, 1563], '50': [1524, 1598, 3740, 3770, 3811, 3867, 3933, 3965, 4004, 4037], '0.1': [1536, 1578], 'phenylmethylsulfonyl': [1538, 1580], 'fluoride,': [1539, 1581], 'loaded': [1543], 'column.': [1548], 'eluted': [1552], 'linear': [1555], 'gradient': [1556], 'B': [1562], 'm': [1567], '6.8).': [1583], 'contained': [1586, 2144], '0.9–1.5': [1587], '15N-': [1589], '15N/13C-labeled': [1591], '95%': [1594], 'H2O,': [1595, 1714], '5%': [1596], 'D2O,': [1597], 'phosphate': [1600], 'buffer,': [1601], '6.8,': [1603], 'dithiothreitol.': [1607], 'Preparation': [1608], 'MTs—Porcine': [1610], 'brain': [1611], 'tubulin': [1612, 4392], '(15Mandelkow': [1617], 'Herrmann': [1619], 'Ruhl': [1621], '1985;': [1626], '185:': [1627], '311-327Crossref': [1628], '(169)': [1631], 'incubated': [1635, 4275], 'concentrations': [1637, 2086, 2166, 3420, 3433, 3637], 'higher': [1638], 'than': [1639, 2426, 2745, 3843, 4278], '200': [1640], 'μm': [1641, 1677, 2174, 2186], '(100': [1646], '6.9,': [1650], 'EDTA,': [1653], 'MgSO4,': [1656], 'dithiothreitol)': [1659], 'GTP': [1666], '37': [1668, 1688, 4253], '°C': [1669, 1745, 2163, 2259, 3741, 3771, 3812, 3868, 3934, 3966, 4005, 4038, 4254, 4391, 4549, 4635], 'After': [1673, 3747, 3780, 3861, 3957, 4250, 4380], 'addition': [1674, 3819, 3846, 3920, 3950, 4024, 4121], '100': [1676, 1736], 'Paclitaxel': [1678], '(Sigma-Aldrich)': [1679], 'performed': [1683, 3710], 'min': [1686], '°C.': [1689, 4220], 'Electron': [1690], 'Microscopy—Proteins': [1691], 'diluted': [1693], 'concentration': [1696, 3655, 3722, 4140], '∼0.1': [1698], 'mg/ml,': [1699], 'placed': [1700], '600-mesh': [1702], 'carbon-coated': [1703], 'copper': [1704], 'grids': [1705], 'min,': [1708], 'washed': [1709], 'drops': [1712], 'negatively': [1716], 'stained': [1717], '2%': [1719], 'uranyl': [1720], 'acetate': [1721], '45': [1723], 's.': [1724], 'specimen': [1726], 'examined': [1728], 'Philipps': [1731], '12M': [1732], 'electron': [1733, 4246], 'microscope': [1734], 'kV.': [1737], 'Spectroscopy—NMR': [1739], 'spectra': [1740, 2082, 2241, 2462, 2530, 2630, 3650, 3974, 4189], 'acquired': [1742], 'Bruker': [1747], 'DRX': [1748, 1753], '800,': [1749], 'Avance': [1750], '600,': [1751], '600': [1754], 'spectrometers.': [1756], 'Aggregation': [1757], 'did': [1758, 4016], 'not': [1759, 2454, 2632, 2890, 3336, 3570, 4017, 4040, 4079, 4287, 4540], 'occur': [1760, 2442], 'under': [1761], 'these': [1762, 1905, 2433, 2528, 2623, 4230, 4600], 'low': [1763], 'temperature': [1764, 3776, 4047, 4099, 4208], 'conditions.': [1765], 'data': [1767, 4059], 'processed': [1769], 'analyzed': [1771, 3688], 'nmrPipe': [1773], '(16Delaglio': [1774], 'F.': [1775], 'Grzesiek': [1776, 2470], 'Vuister': [1778], 'G.W.': [1779], 'Zhu': [1780], 'Pfeifer': [1782], 'Bax': [1784, 2487], 'Biomol.': [1787, 2517, 2559], 'NMR.': [1788, 2518, 2560], '1995;': [1789], '6:': [1790], '277-293Crossref': [1791], '(11837)': [1794], 'Sparky': [1798], 'Three-dimensional': [1800], 'triple-resonance': [1801], 'experiments': [1802, 2507, 4432], 'collected': [1804], 'obtain': [1806], 'sequence-specific': [1807], 'assignments': [1808], 'backbone': [1811, 2281, 2532, 3363], '(supplemental': [1816, 2852], 'Table': [1817], 'S1).': [1818, 2854], 'Secondary': [1819], 'values': [1821, 1874, 2728], 'calculated': [1823, 2208], 'differences': [1826, 2196, 2221, 3995], 'measured': [1829], 'Cα/C′': [1830, 3056, 3177], 'empirical': [1835], 'random': [1836, 2726, 3308], 'coil': [1837, 1873, 2727], 'value': [1838], 'appropriate': [1841], 'amino': [1842, 2420, 2434, 2747], 'acid': [1843, 2421], 'type': [1844, 1975, 3158, 3220], '3.0': [1847], '(17Schwarzinger': [1848], 'Kroon': [1850], 'G.J.A.': [1851], 'Foss': [1852], 'T.R.': [1853], 'Chung': [1854], 'Wright': [1856, 2687], 'P.E.': [1857, 2688], 'Dyson': [1858], 'H.J.': [1859, 2686], 'Am.': [1861, 2490], '123:': [1865, 2494], '2970-2978Crossref': [1866], '(519)': [1869], 'Random': [1872], 'histidines,': [1876], 'glutamates,': [1877], 'aspartates': [1879], 'taken': [1881], 'Wishart': [1883, 1919, 2701], '(18Wishart': [1886, 1922, 1981, 2704], 'D.S.': [1887, 1923, 1982, 2705], 'Sykes': [1888, 1924, 1983, 2706], 'B.D.': [1889, 1925, 1984, 2707], 'Methods': [1890, 1926, 1985, 2708, 3384, 4176], 'Enzymol.': [1891, 1927, 1986, 2709], '239:': [1893, 1929, 1988, 2711], '363-392Crossref': [1894, 1930, 1989, 2712], '(942)': [1897, 1933, 1992, 2715], 'Scholar),': [1899, 1994], 'sensitive': [1909, 2673], 'pH,': [1911], '(pH': [1936, 1946], '5.0)': [1937], 'more': [1939, 2425, 2744, 3593, 4277], 'here': [1945], '6.9).': [1947], 'estimate': [1949], 'β-sheet': [1951, 1979], 'propensity': [1952, 2894, 3067, 3092, 3123, 3170, 3270, 3341], 'contiguous': [1954], 'segments': [1955], 'observed': [1959, 2978, 3316, 3498, 3544, 3599, 3697, 4063, 4643], 'Cα': [1960, 2667, 2751, 2925, 3005, 3108, 3224, 3312], 'normalized': [1964, 1997], 'empirically': [1967], 'determined': [1968], 'expected': [1971], 'residue': [1974, 3186], 'fully': [1978], 'conformation': [1980, 2067], 'summed,': [1995], 'number': [2000], 'segment.': [2005], 'Tau-polyanion': [2006], 'titrations': [2007, 2141, 4215], 'carried': [2009], 'out': [2010], '15N-labeled': [2013, 2150], '0.2': [2016], '(heparin': [2018, 2029], 'titration)': [2019, 2024, 2030, 2035], '0.3': [2021], '(poly-Glu': [2023, 2034], 'K18,': [2025, 2740, 4410], '0.12': [2027], '0.14': [2032, 2147], '6.8.': [2039], 'Heparin': [2040], '(average': [2041, 2054], 'molecular': [2042, 2055, 2372], 'weight': [2043, 2056], '3000,': [2044], '∼5.8': [2045], 'disaccharide': [2046], 'subunits,': [2047], 'charge/subunit': [2048], '∼2.5,': [2049], '∼0.31': [2050], 'z/Å)': [2051, 2069], '10,000,': [2057], '7–8': [2058, 2061], 'Glu': [2059], 'residues,': [2060, 2847], 'negative': [2062, 2750, 2836, 2862, 3055], 'net': [2063], 'charge,': [2064], 'extended': [2066], '0.33': [2068], 'Sigma.': [2072], 'Complex': [2073, 2155], 'monitored': [2076, 2158, 3405], 'recording': [2078], 'two-dimensional': [2079, 4186], '1H-15N': [2080, 2239, 3407, 3648, 3714, 3751, 3972, 4187], 'HSQC': [2081, 2240, 3408, 3649, 3715, 3794, 3973, 4188], 'increasing': [2084, 2445, 3418, 3653, 4200, 4403, 4415, 4519], 'polyanion': [2085, 3419, 3432, 3636, 3654, 3680, 4074], '(in': [2087], 'mm):': [2088], '0.03,': [2089, 2102, 2116, 2128], '0.06,': [2090], '0.15,': [2091], '0.3,': [2092], '0.58,': [2093], '1.37,': [2094], '2.53': [2096], '(K18': [2097, 2111], 'heparin),': [2099, 2125], '0.008,': [2100, 2114], '0.015,': [2101, 2115, 2127], '0.072,': [2103], '0.142,': [2104], '0.28,': [2105, 2119], '0.68,': [2106], '1.3,': [2107], '2.4,': [2108], '4.3': [2110], 'poly-Glu),': [2113], '0.07,': [2117], '0.14,': [2118], '0.67,': [2120], '1.3': [2122], '(K19': [2123, 2136], '0.074,': [2129], '0.146,': [2130], '0.29,': [2131], '0.70,': [2132], '1.35,': [2133], '2.49': [2135], 'poly-Glu).': [2138], 'tau-MT': [2140], '0.13': [2145], 'K19,': [2153, 2250, 3562], 'respectively.': [2154, 3032, 3990], '(αβ-tubulin': [2167], 'dimers)': [2168], '26.5,': [2170], '79.5,': [2171], '159.0': [2173], 'titrations,': [2178], '2.8,': [2180], '5.4,': [2181], '20.0,': [2182], '35.0,': [2183], '84.3': [2185], 'titration.': [2190, 3701], 'Normalized': [2191], 'weighted': [2192], 'average': [2193, 4011], 'amide': [2198, 2941, 3476], '1H': [2199], 'upon': [2204, 3845, 4023, 4127], 'polyanion/MT': [2205], 'Δav(NH)': [2210], '[(ΔH2': [2212], '(ΔN/5)2)/2]1/2,': [2214], 'where': [2215, 3102], 'ΔH': [2216], 'ΔN': [2218], 'free': [2224, 4021], 'bound': [2226, 4132, 4525, 4529], 'shifts.': [2228], 'Backbone': [2229, 2384], 'Resonance': [2230], 'Assignment': [2231, 2366], '—NMR': [2236], 'resonances': [2237, 2264, 2363, 2403, 2617, 3477, 3633, 4554, 4622], '15N,': [2254, 2643], 'recorded': [2256, 4195], '6.9.': [2262], 'sharp': [2266], 'showed': [2268], 'limited': [2271, 2399, 3097], 'dispersion': [2272, 2400], 'shifts,': [2275, 2663, 3058], 'reflecting': [2276], 'mobility': [2282], 'nature,': [2285], 'agreement': [2287, 3128, 4459, 4591], 'FTIR': [2291], 'measurements': [2292], '13von': [2313], 'enable': [2345], 'study': [2347], 'dynamics': [2352], 'atomic': [2356], 'resolution,': [2357], 'assignment': [2359, 2385, 2452, 2534, 2549, 2571], 'required.': [2365], 'globular': [2368, 2680], 'mass': [2373], 'below': [2374], '15': [2375], 'kDa': [2376], 'straightforward': [2378], 'today': [2379], 'techniques.': [2383], '(130': [2388], 'residues)': [2389, 2393], '(99': [2392], 'complicated,': [2395], 'however,': [2396], 'because': [2404, 2891, 2900, 2958, 3079, 3670, 4068, 4080, 4542], 'absence': [2407, 2938], 'defined': [2410], 'tertiary': [2413], 'elements.': [2415], 'In': [2416, 2736, 2832, 2882, 2946, 3244, 3463, 3491, 3561, 3590, 4008, 4304, 4505, 4590], 'addition,': [2417, 3492, 3591, 4009, 4506], 'five': [2419, 3802], 'types': [2422, 3556], 'make': [2423], 'up': [2424, 4032], '50%': [2427, 3682], 'primary': [2430], 'sequence,': [2431], 'acids': [2435], 'arranged': [2437], 'repetitively,': [2443], 'further': [2444, 3196], 'signal': [2447, 3644, 3903, 3969], 'overlap.': [2448], 'unambiguous': [2451], 'possible': [2455, 2609], 'just': [2456, 4611], 'relying': [2457, 2573], 'conventional': [2460], 'three-dimensional': [2461, 2503], 'HNCO,': [2463], 'HN(CA)CO,': [2464], 'HNCACB': [2465], 'CBCA(CO)NH': [2467], '(19Bax': [2468], 'Acc.': [2472], 'Res.': [2474], '26:': [2476], '131-138Crossref': [2477], '(800)': [2479], '(HA)CANNH': [2484], '(20Zweckstetter': [2485], '9490-9491Crossref': [2495], '(63)': [2498], 'together': [2501], 'HNN': [2504, 2576], 'HN(C)N': [2506], 'required': [2509], '(21Panchal': [2510], 'S.C.': [2511], 'Bhavesh': [2512], 'N.S.': [2513], 'Hosur': [2514], 'R.V.': [2515], '20:': [2520], '135-147Crossref': [2521], '(176)': [2524], 'With': [2527], 'resonance': [2533], 'achieved': [2541], 'iterative': [2544], 'fashion': [2545], 'automatic': [2548], 'program': [2552], 'MARS': [2553], '(22Jung': [2554], 'Y.S.': [2555], 'Zweckstetter': [2556], '30:': [2562], '11-23Crossref': [2563], '(241)': [2566], 'manual': [2570], 'mainly': [2572, 4559], 'experiment.': [2577], 'motif': [2580, 3153], 'PGGG,': [2581], 'located': [2584, 4604], 'characteristically': [2585], 'each': [2591, 3040, 4579, 4609], 'repeats,': [2595], 'caused': [2596], 'biggest': [2598], 'problems.': [2599], 'severe': [2602], 'overlap,': [2605], 'assign': [2611], 'Gly273,': [2612], 'Gly304,': [2613], 'Gly335.': [2615], 'remaining': [2620, 3344], 'glycines': [2621, 3105], 'within': [2622], 'identified': [2627, 3174], 'unambiguously': [2633], 'assigned': [2634, 2651], 'repeats.': [2639, 3117], 'Otherwise,': [2640], '1H,': [2642], '13Cα,': [2644], '13Cβ,': [2645], '13C′': [2647], 'both': [2653, 2678, 2730, 4452], 'K19.': [2656, 4430], 'Soluble': [2657], 'Contains': [2659], 'Residual': [2660], 'β-Structure—NMR': [2661], 'particular': [2665], 'C′': [2669, 2912, 3007, 3110, 3226], 'atoms,': [2670], 'very': [2672, 3856, 4544], 'probes': [2674, 3367], '(Ref.': [2684], '23Dyson': [2685], 'Nat.': [2689], 'Struct.': [2690], '5:': [2693], '499-503Crossref': [2694], '(214)': [2697], 'Scholar': [2699], 'small': [2721], 'distinct': [2723], 'deviations': [2724], '(Fig.': [2734, 2774, 2989, 3011, 3086, 3193, 3461, 3489, 3545, 3617, 4248, 4299, 4356, 4375, 4400, 4423, 4574], '2).': [2735], 'case': [2738, 2833, 2884, 2948, 3465], 'continuous': [2741], 'stretches': [2742, 2777], '(containing': [2743], 'acids)': [2748], 'Lys274-Leu284,': [2759], 'Ser305-Leu315,': [2760], 'Gln336-Asp345': [2762], '(numbering': [2763], 'according': [2764], 'longest': [2767], 'htau40),': [2769], 'indicative': [2770, 4516], 'nascent': [2772], '2A).': [2775], 'lie': [2778], 'R2,': [2784], 'R3,': [2785], 'R4,': [2787], 'downstream': [2788, 3162], 'PGGG': [2790, 3100, 3152, 4615], 'encompass': [2793], 'hexapeptide': [2795], 'VQIINK': [2797], 'VQIVYK': [2799], 'important': [2803, 3611], '(8von': [2812], 'C′,': [2835], 'detected': [2841], 'range': [2845], 'Gly273-Leu282,': [2848], 'Gly304-Asp314,': [2849], 'Gly335-Asp345': [2851], 'It': [2855], 'notable': [2857], 'preponderance': [2860], 'persists': [2866], 'even': [2867, 2981], 'less': [2873, 3842], 'homologous': [2874], 'R1': [2876, 2886, 3139], 'Ala246-Leu253)': [2878], 'R5': [2880, 2950, 2967], '(Asn368-Ile371).': [2881], 'this': [2887, 2918, 3775, 4285], 'likely': [2889, 3665], 'rather': [2899, 3898], 'occurrence': [2903], 'prolines': [2906, 2930], '(Pro247,': [2907], 'Pro249,': [2908], 'Pro251).': [2909], 'Indeed,': [2910], 'alternated': [2916], 'consistent': [2920], 'fact': [2923, 3131], 'atoms': [2926], 'preceding': [2929], 'unusual': [2932], 'due': [2935, 3666], 'proton': [2942], 'proline.': [2945], 'results': [2952, 4462], 'must': [2953], 'viewed': [2955], 'caution': [2957], '(not': [2968], 'counting': [2969], 'residue).': [2972], 'remarkably': [2974], 'pattern': [2976, 3315, 3538], 'though': [2982], '(exon': [2985], '10)': [2986], 'absent': [2988], '2C),': [2990], 'suggesting': [2991], 'independent': [2996], 'units.': [2998], 'quantitative': [3000, 4360], 'analysis': [3001, 3672, 4050, 4271, 4361], 'averaged': [3004], '2B)': [3012], 'indicates': [3013, 3119, 3327, 4577], 'β-structure-like': [3015], 'conformations': [3016], 'populated': [3018], '∼16,': [3019], '24,': [3020], '13%': [3022], 'time': [3025, 3459, 4015, 4441], 'Lys274-Asp283,': [3028], 'Ser305-Asp314,': [3029], 'Gln336-Asp345,': [3031], 'Besides': [3033], '295KDNIK299': [3043], '357LDNIT361': [3045], 'R4': [3050], 'stretch': [3053], 'indicating': [3059, 3451, 3547], 'propensity.': [3062, 3243, 3265], 'Note': [3063], '3': [3076], '(325LGNIH329),': [3077], 'possibly': [3078], 'glycine': [3085], '2B).': [3087, 3194], 'upstream': [3098], 'motifs,': [3101], 'This': [3118, 3326, 3798, 4576], 'turn,': [3126], 'GGK': [3133], 'GGS': [3135], '(present': [3137], 'R2)': [3141], 'most': [3144, 3172, 3267, 3837, 4495, 4551, 4637], 'common': [3145, 3156, 3218], 'classic': [3148], 'γ-turns.': [3149], 'Alternatively,': [3150], 'II': [3159], 'β-turns.': [3160], 'prominently': [3173], '10th': [3183], 'and/or': [3184], '11th': [3185], '2–4': [3189, 3253], '(Ser285,': [3190], 'Ser316,': [3191], 'Phe346)': [3192], 'Taking': [3195], 'account': [3198], 'dyads': [3201], '285SN286': [3204], '316SK317': [3206], '(the': [3207], 'following': [3209], 'β-propensity': [3211], 'R3)': [3216], 'I': [3221], 'β-turns,': [3222], 'suggest': [3230], 'β-turn': [3232], 'conclusion,': [3245], 'sandwiched': [3258], 'turn': [3264], 'pronounced': [3268, 3594, 4638], 'N': [3275], 'terminus': [3276], 'whereas': [3281], 'fourth': [3286], 'approximately': [3290], 'factor': [3292], '1.5–2': [3294], 'lower.': [3295], 'β-conformations': [3297], 'presumably': [3303], 'rapid': [3305], 'like': [3309], 'structures.': [3310], 'almost': [3320, 3872], 'identical': [3321], 'K18.': [3325], 'removal': [3330], 'does': [3335, 4286], 'affect': [3337], 'local': [3339], 'part': [3345, 4107], 'tau.': [3351], 'Characterization': [3352], 'Its': [3358], 'Polyanion': [3359], 'Complexes—NMR': [3360], 'signals': [3361, 4534], 'amides': [3364], 'constitute': [3365], 'excellent': [3366], 'complex': [3369], 'formation,': [3370], 'providing': [3371], 'maps': [3372], 'interfaces': [3376], 'constants': [3379], '(24Craik': [3380, 4172], 'Wilce': [3382, 4174], 'J.A.': [3383, 4175], '1997;': [3387, 4179], '60:': [3388, 4180], '195-232PubMed': [3389, 4181], 'heparin': [3397, 3467, 3724, 3754, 3821, 3848, 3922, 3952, 4026, 4092, 4129, 4142], 'spectra.': [3409], 'size': [3411], 'depends': [3421], 'strength': [3425], 'residues.': [3429], 'At': [3430, 3907, 4042, 4547, 4633], 'accompanied': [3441], 'decrease': [3444], 'intensity': [3447, 3645, 3904, 3970], 'their': [3449], 'signals,': [3450], 'intermediate': [3455], 'scale': [3460], '3).': [3462, 3956], 'exhibiting': [3470], 'displacements': [3473], 'Val275-Leu284': [3481], '4A).': [3490], 'strong': [3493, 3857], 'environment': [3501, 4562], 'selected': [3503, 4487], 'lysine': [3504, 3517, 3580, 4564, 4619], 'histidine': [3506, 3519, 3582, 4566], 'residues:': [3507, 4567], 'Leu253-Lys254,': [3508, 4568], 'His268-Gln269,': [3509, 4569], 'Lys298-Val300,': [3510, 4570], 'His329-Lys331,': [3511, 4571], 'His362.': [3513], 'importance': [3515], 'suggests': [3521], 'electrostatically': [3528], 'driven.': [3529], 'Upon': [3530], 'titration': [3531, 3681, 4048], 'poly-Glu,': [3535], '4B),': [3546], 'overall': [3550, 3643, 3900, 3968], 'behavior': [3552, 3695], 'similar.': [3560], 'missing': [3566], 'therefore': [3569], 'contribute': [3571], 'polyanions.': [3576], 'However,': [3577], 'strongly': [3588, 4496, 4552], 'affected.': [3589], 'slightly': [3592], 'Val306-Lys311,': [3601], '4,': [3618, 3958], 'C': [3619], 'D).': [3621], 'Concomitant': [3622], 'disappearance': [3630, 4492], '(caused': [3638], 'ligand': [3640], 'binding),': [3641], 'decreased': [3651, 3976, 4511], '(after': [3656], 'correction': [3657], 'dilution': [3659], 'effects).': [3660], 'latter': [3662], 'effect': [3663, 3705], 'partial': [3668], 'biochemical': [3671, 4049], 'indicated': [3673, 4051], 'polymerized,': [3686], 'pelleting': [3690], 'SDS-PAGE.': [3692], 'K19-poly-Glu': [3700], 'investigate': [3703], 'further,': [3708], 'series': [3712], 'spectra,': [3716], 'ratio': [3720, 3759, 3938, 4104, 4509], '(1:4)': [3727], 'held': [3729], 'constant,': [3730], 'sample': [3733, 3766, 3785, 4273], 'kept': [3735, 3773, 3809], 'variable': [3737], 'times': [3738, 4095], 'induce': [3743], 'accelerate': [3745], 'aggregation.': [3746, 4082], 'measurement': [3748, 4446], 'HSQCs': [3752], 'heparin:K18': [3758, 3937, 4103], '1:4': [3761, 3940], '°C,': [3764, 3791, 4283, 4502, 4627], 'heated': [3768], 'h.': [3779], 'h': [3783, 3815, 3865, 3931, 3963, 4002, 4035, 4280], 'cooled': [3787], 'down': [3788], 'spectrum': [3795, 3883, 3928, 3987, 3999], 'recorded.': [3797], 'procedure': [3799], 'repeated': [3801], 'times,': [3803], '10': [3814, 3962, 4034], 'total.': [3817], 'induced': [3822, 3918, 4119], 'reported': [3829], '4.': [3832], 'peak': [3834], 'intensities': [3835, 3870], 'reduced': [3840, 3876], '15%': [3844], 'exception': [3851], 'those': [3853], 'showing': [3855], 'changes.': [3860], 'first': [3863], 'peaks': [3874], '72%': [3878], 'compared': [3879, 3983, 4019], 'starting': [3882, 3986], 'heparin.': [3885], 'There': [3886], 'area': [3889], 'affected': [3895, 4624], 'strongly,': [3897], 'loss': [3901], 'observed.': [3906, 4007, 4504], 'time,': [3910], 'initially': [3917], 'lost,': [3925], 'i.e.': [3926], 'after': [3929, 4000, 4028], 'before': [3949], '(shown': [3953], '6,': [3959], '8,': [3960], 'continuously': [3975], '68,': [3978], '65,': [3979], '64,': [3980], '61%': [3982], 'No': [3991], 'large': [3992], 'relative': [3996], 'transverse': [4012], 'relaxation': [4014], 'change': [4018, 4320], 'keeping': [4029], '(data': [4039], 'shown).': [4041], '∼50%': [4053], 'polymerized.': [4057], 'indicate': [4060], 'When': [4083, 4402, 4528], 'exposed': [4087], 'levels': [4090], 'prolonged': [4094], 'constant': [4102], '1:4,': [4106], 'aggregated.': [4111], 'As': [4112], 'changes,': [4116], 'removed': [4126], 'may': [4130], 'become': [4131, 4314], 'aggregates,': [4135], 'reducing': [4137], 'effective': [4139], 'solution.': [4144], 'Binding': [4146], 'Mode': [4147], 'Polyanions': [4151], 'Is': [4154], 'Similar—The': [4155], 'method': [4171], 'amounts': [4201, 4404, 4416], 'taxol-stabilized': [4203, 4227, 4436], 'MTs.': [4204, 4527, 4589], 'probed': [4210], 'performing': [4212], 'ascertain': [4222], 'temperatures,': [4231], 'aliquots': [4232], 'reactions': [4235], 'sedimentation,': [4243], 'SDS-PAGE,': [4244], 'microscopy': [4247], '5).': [4249], 'exhibit': [4257], 'typical': [4259], 'morphological': [4260], 'features': [4261, 4311], 'protofilaments': [4263], 'spaced': [4264], '∼5': [4265], 'nm': [4266], 'apart.': [4267], 'During': [4268], 'lead': [4288], 'disintegration': [4291], 'taxol': [4298, 4384], '5,': [4300, 4376], 'B).': [4303], 'surface': [4310], 'somewhat': [4315], 'fuzzier': [4316], 'subunit': [4322], 'arrangement': [4323], 'Santarella': [4325], 'al.,': [4327], '2004': [4328], '(39Santarella': [4329], 'R.A.': [4330], 'Skiniotis': [4331], 'Goldie': [4333], 'K.N.': [4334], 'Tittmann': [4335], 'Gross': [4337], 'Hoenger': [4343], '339:': [4349], '539-553Crossref': [4350], '(124)': [4353], '5C).': [4357], 'centrifuged,': [4365], 'supernatants': [4368], 'checked': [4372], 'SDS-PAGE': [4374], 'D': [4377], 'E).': [4379], 'incubation': [4386], 'mostly': [4395], 'pellet': [4398, 4421], 'fraction': [4399, 4422], '5D).': [4401, 4424], 'added': [4408], 'resulted': [4413], 'true': [4428], 'persist': [4438], 'over': [4439], 'course': [4442], 'parameters': [4450], 'good': [4458], 'earlier': [4461], 'Continuous': [4482], 'followed': [4489], 'shifting': [4497, 4553], 'resonances,': [4498], 'especially': [4499], 'signal:noise': [4508], 'rapidly': [4510], 'concentrations,': [4515], 'amount': [4520], 'MTs,': [4531], 'observable': [4541], 'fast': [4545], 'relaxation.': [4546], 'His362': [4573], '6A).': [4575], 'site': [4584], 'anchoring': [4586], 'repetitive': [4594], 'region,': 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