Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on <scp>MAP</scp> kinases

Name: Work Video:
Duration: 3 min 30 s
András Zeke; Tomas Bastys; Anita Alexa; Ágnes Garai; Bálint Mészáros; Klára Kirsch; Zsuzsanna Dosztányi; Olga V. Kalinina; Attila Reményi
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2889], 'hindered': [682], 'because': [683, 2513], 'MAPKs': [684, 810, 969, 3328, 3431, 3535], 'bind': [685, 912, 1205, 2235, 2473, 3410, 4081], 'other': [687, 766, 828, 1024, 1576, 1662, 3395, 4018], 'proteins': [688, 966, 1020, 1139, 1769, 2423, 2967, 2978, 3018, 3060, 3111, 3722, 3959], 'with': [689, 793, 825, 1154, 1159, 1468, 1934, 2148, 2172, 2273, 2333, 2432, 2467, 2476, 2556, 2560, 2607, 2696, 2877, 2903, 3015, 3424, 3728, 3925, 4145, 4197, 4212], 'low': [690, 1857, 1928, 2019, 3150], 'affinity': [691, 2478, 4123, 4223], 'mostly': [693, 995], 'less-characterized': [695], 'disordered': [696, 870, 895, 1001, 1073, 1233], 'regions.': [697, 1003], 'We': [698, 861, 3373], 'structurally': [701, 718, 1527, 2105, 2266], 'consistent': [702], 'model': [703, 2859], 'kinase-docking': [705], 'motif': [706, 908, 1348, 1651, 1682, 1704, 2454, 2584, 2705, 2829, 2870, 2970, 3271, 3318, 3323, 3469, 3793, 3826, 3832, 3879, 3936, 3997], 'interactions': [707, 738, 1006, 1092, 2184], 'facilitate': [709], 'short': [713, 864, 906, 1056, 1135, 1215, 1565, 1572, 2809, 3799], 'functional': [714, 1068, 3153], 'sites': [715, 822, 920, 1069, 1181, 1240, 3107], 'flexible': [719], 'functionally': [721, 785, 962], 'under-explored': [722], 'part': [723, 896], 'human': [726, 818, 843, 899, 954, 1112, 2355, 2474, 2977, 3497, 4034], 'proteome': [727, 900, 1113, 3498], 'applied': [729, 2667], 'experimental': [730, 752, 938, 1882, 1958, 2174, 2952, 2995], 'tools': [731], 'specifically': [732], 'tailored': [733, 2040, 2173], 'detect': [735, 3029, 3442], 'low-affinity': [736, 2180, 3030], 'protein–protein': [737, 768, 1144, 1337, 2029, 2183], 'their': [740, 1142, 1151, 1164, 1296, 1311, 1545, 2346, 2928], 'validation': [741, 2178], 'vitro': [743], 'cell-based': [746], 'assays.': [747], 'The': [748, 771, 838, 894, 956, 1175, 1357, 1427, 1519, 2546, 2850, 3165, 3200, 3700, 3870, 3976, 4203], 'combined': [749, 935], 'computational': [750, 936], 'approach': [753, 939, 1996], 'enabled': [754, 2860], 'identification': [756, 2160], 'many': [758], 'novel': [759, 2162, 2726, 3444, 3466, 3758, 4011], 'MAPK-docking': [760, 1355, 1358, 1681, 2215, 2336, 2727, 2880, 2933, 4063, 4084, 4099], 'that': [762, 826, 841, 863, 910, 1099, 1132, 1690, 1720, 1801, 1943, 1964, 1992, 2027, 2096, 2131, 2136, 2286, 2330, 2388, 2586, 2635, 2709, 2786, 3008, 3267, 3472, 3488, 3704, 3763, 3858, 4046], 'were': [763, 1764, 1898, 2427, 2628, 2636, 2652, 2805, 2939, 2947, 3112, 3276, 3355, 3420, 3439, 3945, 4050, 4072], 'elusive': [764], 'large-scale': [767, 1861, 1905], 'screens.': [770], 'analysis': [772, 839, 2169, 2822, 3256], 'produced': [773, 2185], 'extensive': [775, 1848], 'list': [776], 'independently': [778], 'evolved': [779, 835], 'from': [783, 1137, 1219, 1237, 1388, 1503, 1770, 1798, 2037, 2222, 2229, 2352, 2462, 2757, 2968, 3088, 3278, 3290, 3302, 3358, 3470], 'diverse': [786, 963, 1289], 'set': [787, 964, 2486, 4066], 'proteins.': [789, 1212, 1272, 2817], 'These': [790, 916, 1067, 1372, 1462, 1674, 2411, 3958], 'all': [791, 1008, 2366, 2670, 2685, 3326, 3523, 3898, 4005], 'target,': [792], 'characteristic': [794, 2457], 'specificity,': [796], 'evolutionarily': [803, 849], 'related': [804, 3478], 'but': [805, 1158, 1544, 1632, 2104, 2559, 3915, 4020], 'physiologically': [806], 'clearly': [807], 'distinct': [808, 1362, 1529, 2106, 2209], 'three': [809, 1432, 1523, 3279, 3327, 3430, 3534], '(JNK,': [811], 'ERK,': [812], 'p38).': [814], 'This': [815, 1029, 1794, 2078, 2168, 2574, 2665, 2920, 3237, 3386, 4010, 4025], 'inventory': [816], 'kinase': [820, 945, 1165], 'was': [823, 1096, 1796, 1866, 1962, 1986, 2536, 2549, 2576, 2659, 2666, 2712, 2737, 2823, 3042, 3076, 3149, 3250, 3387], 'compared': [824, 2386, 3124], 'organisms': [829], 'examine': [831], 'kinase-mediated': [833], 'partnerships': [834], 'over': [836, 983], 'time.': [837], 'suggests': [840], 'most': [842, 1015, 1176, 1294, 1890, 2780, 3717], 'MAPK-binding': [844, 865, 1768, 2202, 3965], 'surprisingly': [847], 'new': [848, 890, 931], 'inventions': [850], 'newly': [852], 'found': [853, 1230, 1257, 3421, 3464, 3475, 4014], 'links': [854], 'highlight': [855], '(previously': [856], 'hidden)': [857], 'roles': [858, 2191], 'MAPKs.': [860, 3411], 'propose': [862], 'stretches': [866], 'created': [868], 'segments': [872, 1136, 2643, 2785, 3800], 'through': [873, 1018, 2749, 3191], 'variety': [875, 1269, 1500], 'ways': [877], 'they': [879, 1203, 1292, 2426, 3771, 3990], 'represent': [880, 921], 'major': [882, 923, 1557], 'resource': [883, 924], 'signaling': [886, 927], 'acquire': [889, 930], 'regulatory': [891, 932], 'roles.': [892, 933], 'Synopsis': [893], 'contains': [901, 3240, 4210], 'large': [903, 2508, 2980], 'number': [904, 2020, 2064, 2509, 2527, 2964, 3484], 'occurrences': [909, 2585], 'kinases.': [915], 'simple': [917, 3009], 'protein-protein': [918], 'recruitment': [919], 'A': [934, 1615, 1737, 2304, 3228, 3878], 'identifies': [940], 'hundreds': [941], 'putative': [943, 2541], 'motifs—referred': [949], 'as': [951, 985, 1780, 2153, 2356, 2415, 2790, 2808, 2815, 2942, 3013, 3081, 3083, 3706, 3770, 3882, 3939, 3947], 'D(ocking)-motifs—in': [952], 'proteome.': [955], 'wide': [957], 'distribution': [958], 'D-motifs': [960, 994, 1213, 1489, 1779, 1802, 2097, 2163, 2221, 2262, 2269, 2344, 2853, 3080, 3164, 3489, 4059], 'explains': [967], 'regulate': [971], 'processes.': [977], 'based': [979, 1677, 2012, 2854, 3043, 3379, 3446], 'interactomes': [980], 'changed': [981], 'fast': [982], 'time': [984], 'D-motif': [986, 1336, 2210, 3154, 3818, 3848, 3895], 'composition': [987], 'vertebrate': [989], 'proteomes': [990, 1772], 'remarkably': [992], 'different.': [993], 'emerge': [996], 'random': [998], 'mutations': [999], 'Introduction': [1004], 'Protein–protein': [1005, 1046], 'influence': [1007, 1022], 'aspects': [1009], 'life': [1012], 'direct': [1016, 1983, 2014], 'mechanism': [1017], 'which': [1019, 1054, 2042, 2425, 2676, 2887, 3041, 3090], 'each': [1023, 1469, 1706, 2969, 3126, 4152], 'physical': [1027, 1984, 2015], 'interaction.': [1028], 'brings': [1030], 'them': [1031], 'into': [1032, 2044, 2189, 3802, 4061], 'proximity': [1033], 'exert': [1035], 'control': [1036, 1288, 3540, 3923, 4077], 'activity': [1038], 'or': [1039, 1300, 1494, 1605, 1620, 1748, 1818, 1980, 2006, 2112, 2314, 2594, 2644, 3019, 3137, 3335, 3434, 3830, 4199, 4221], 'create': [1041], 'opportunities': [1042], 'posttranslational': [1044], 'modification.': [1045], 'associations': [1047], 'often': [1048, 4219], 'involve': [1049], 'so-called': [1050, 1207], '(5–20': [1057], 'amino': [1058, 1223, 1434, 1725, 1755, 2292, 2320, 2610, 2984], 'acid': [1059, 2611, 3795], 'long)': [1060], 'regions': [1062, 1075, 1689, 2435, 2555, 2675], 'lacking': [1063], 'autonomous': [1064], 'tertiary': [1065], 'structure.': [1066], 'reside': [1070], 'intrinsically': [1072, 1232], 'adopt': [1077, 2617], 'stable': [1078, 2619], 'conformation': [1079, 2447], 'only': [1080, 1086, 1250, 1554, 1636, 1856, 3859], 'upon': [1081, 2621], 'binding.': [1082, 1702], 'Currently,': [1083], 'we': [1084, 2129, 2484, 2707, 2884, 2961, 2999, 3036, 3347, 3438, 3462], 'guess': [1087], 'abundant': [1089], 'motif-based': [1091], 'are;': [1093], 'nevertheless,': [1094], 'it': [1095, 1781, 2024, 2081, 2093, 2602, 3714, 3889, 3903, 3928], 'recently': [1097], 'estimated': [1098], 'there': [1100], '~100,000': [1102], 'dedicated': [1107, 1143], 'surfaces': [1109, 1162], '(Tompa': [1114], 'et': [1115, 1168, 1197, 1242, 1396, 1419, 1645, 1791, 1840, 1870, 1874, 1878, 1908, 1912, 1916, 1950, 1975, 2003, 2009, 2075, 2118, 2122, 2247, 2251, 2255, 2369, 2373, 2408, 2440, 2480, 2567, 2571, 2917, 3098, 4037], 'al,': [1116, 1169, 1198, 1243, 1397, 1420, 1646, 1792, 1841, 1871, 1875, 1879, 1909, 1913, 1917, 1951, 1976, 2004, 2010, 2076, 2119, 2123, 2248, 2252, 2256, 2370, 2374, 2409, 2441, 2481, 2568, 2572, 2918, 3099, 4038], '2014).': [1117, 1842], 'As': [1118, 2868, 3054, 3103, 3456], 'example': [1120], 'relevant': [1121], 'signaling,': [1124], 'mitogen-activated': [1125], '(MAPKs)': [1128], 'prototypical': [1130], 'depend': [1133], 'partner': [1138], 'hot': [1146], 'spots.': [1147], 'They': [1148, 1254], 'mainly': [1149], 'recognize': [1150], 'substrates': [1152, 1297, 1903, 1926, 1948, 1973, 3206, 3528], 'catalytic': [1156, 1312], 'site': [1157, 1313, 3087, 3096, 3148], 'auxiliary': [1160, 2657, 2763], 'docking': [1161, 1180, 1186, 1246, 1366, 1429, 2239, 2358, 2453, 3141, 3224, 3235, 3749], 'domains': [1166, 2593], '(Tanoue': [1167], '2000;': [1170], 'Biondi': [1171], 'Nebreda,': [1173], '2003).': [1174], 'important': [1177, 2781], 'consists': [1182], 'hydrophobic': [1185, 1370, 1428, 1433, 1724, 1825, 2291, 4242], 'groove': [1187, 1359, 1401, 1430, 2216, 4085], 'negatively': [1190, 1409], 'charged': [1191, 1410, 1746, 1811, 2312, 4234], 'CD': [1192, 1400, 1484, 2378], '(common': [1193], 'docking)': [1194], 'region': [1195, 2379], '(Chang': [1196], '2002)': [1199], '(Fig': [1200, 2217, 2242, 2405, 2498, 2544, 3052, 3101, 3155, 3367, 4086], '1A).': [1201], 'Together,': [1202], 'D(ocking)-motifs': [1208], 'target': [1211, 1238, 1318, 2039, 3095, 3147], 'ranging': [1218], '7': [1220], '18': [1222], 'acids': [1224, 1435], 'length': [1226, 1453, 1838], 'typically': [1229, 2288], 'segments—potentially': [1234], 'far': [1235], 'away': [1236], 'phosphorylation': [1239, 3046, 3086, 3144, 3169, 3182, 4048], '(Garai': [1241, 1395, 1644, 2074, 2407], '2012).': [1244, 1398, 2077, 2257, 2410, 4039], 'Such': [1245, 3481], 'elements': [1247, 3966], 'restricted': [1251], 'substrates:': [1253], 'also': [1256, 1537, 1625, 1670, 2264, 2436, 2456, 2485, 2603, 2940, 3374, 3463, 3474, 3839, 3876, 4110, 4155], 'MAPK-activating': [1259], '(MAP2Ks),': [1261], 'MAPK-inactivating': [1263], 'phosphatases': [1264], '(MKPs),': [1265], 'scaffold': [1271, 2225], 'While': [1273], 'extracellularly': [1274], 'regulated': [1275], '(ERK1-2),': [1277], 'c-Jun': [1278], 'N-terminal': [1279, 1687], '(JNK1-3),': [1281], '38-kDa': [1284], '(p38α-δ)': [1287], 'processes,': [1291], 'phosphorylate': [1293], 'at': [1298, 1482, 1766, 1806, 2448, 3425, 3909, 3982, 4082], 'Ser-Pro': [1299], 'Thr-Pro': [1301], '(S/TP)': [1302], 'sequence': [1303, 2090, 3381, 3404, 3843, 3953, 3977, 4026, 4139], 'motifs.': [1304, 3072, 3236, 3385], 'Naturally,': [1305], 'weak': [1307], 'consensus': [1308, 1546, 1777, 1795, 2278, 2583, 3774, 3987], 'provided': [1309], 'insufficient': [1315], 'selective': [1317], 'recognition,': [1319], 'additional': [1321, 2155, 3376], 'provide': [1325], 'specificity': [1326, 1457], '(Johnson': [1327], 'Lapadat,': [1329], '2002;': [1330], 'Bardwell,': [1331], '2006).': [1332, 2375, 2442], 'Therefore,': [1333, 2483, 3035], 'system': [1339], 'ideal': [1342], 'test': [1343, 3392, 4107], 'bed': [1344], 'discovery.': [1349], 'Figure': [1350, 2719, 2843, 3159, 3513, 3782, 4119], '1.': [1351, 3550], 'Structural': [1352, 1515], 'classification': [1353, 2851], 'comprises': [1360], 'two': [1361, 1441, 1463, 1556, 2398, 3725, 3984, 4187], 'regions:': [1363], 'common': [1365, 2275], '(CD)': [1367], 'region.': [1371], 'colored': [1374], 'blue': [1376, 4238], 'light': [1378], 'brown,': [1379], 'respectively,': [1380], 'shown': [1383, 1477, 1676, 1709, 3330, 3866], 'JNK1': [1386, 2001, 4194], 'JNK1-NFAT4': [1390], 'protein–peptide': [1391, 2892, 2900, 3033], 'complex': [1392, 2070, 2206, 2912], 'crystal': [1393, 1697], 'structure': [1394, 2620, 3202], '(The': [1399, 3312], 'extended': [1403], 'ED': [1406], 'region,': [1407], 'extra': [1408], 'residues': [1411, 1826, 4230, 4236], 'ERK': [1413, 1619, 2381], 'p38;': [1415], 'see': [1416], '(C);': [1417], 'Tanoue': [1418], '2001.)': [1421], 'Different': [1422], 'modes': [1424, 2212, 2348], 'D-motifs.': [1426, 1518, 1532], 'binds': [1431], 'row,': [1438], 'while': [1439, 1750, 2793, 3751, 3856], 'admitting': [1440], 'different': [1442, 1896, 1941, 3039, 3350, 3973], 'spacing': [1443], 'schemes.': [1444], 'At': [1445], 'same': [1447, 2238, 3216, 3284, 3304], 'time,': [1448], 'θ': [1449, 1742, 1815, 2309, 4235], 'φ': [1451, 4241], 'linker': [1452, 1834], 'determines': [1454], 'given': [1460, 1666, 2335, 2340, 3119], 'motif.': [1461], 'features': [1464, 1525], 'combine': [1466], 'freely': [1467], 'other,': [1470, 2646], 'resulting': [1471], 'four': [1474], 'basic': [1475], 'arrangements': [1476], 'here.': [1478], 'Distinct': [1479], 'conformations': [1481], 'groove.': [1485, 2934], 'N-termini': [1486, 2392], 'longer': [1488, 1592, 1601, 1611, 1628, 2433], 'variable': [1491, 1524, 1837], 'ERK2-': [1493, 4214], 'p38α-binding': [1495, 4216], 'peptides': [1496, 1583, 2466, 4071, 4078, 4108, 4211], 'may': [1497, 1584, 2263, 2349, 2516], 'take': [1498], 'conformations—ranging': [1502], 'fully': [1504], '(e.g.,': [1506, 1512, 1931, 2649], 'MEF2A,': [1507, 3451], 'green)': [1508], 'highly': [1510], 'alpha-helical': [1511], 'HePTP,': [1513], 'magenta).': [1514], 'heterogeneity': [1516], 'combinations': [1520, 4006], 'yield': [1526], 'well-defined,': [1528], 'classes': [1530, 2100], 'Many': [1533], 'models': [1536], 'define': [1538], 'separate': [1539], 'types': [1540, 1558], 'motifs,': [1543, 1560, 2493, 2728, 2792, 3142, 3750], 'sequences': [1547, 1966, 2329, 2515, 3552, 3796, 3813], 'always': [1550, 1804, 2873], 'exclusive.': [1551], 'JNK': [1552], 'admit': [1555], 'NFAT4': [1562, 2234, 3270, 3671], 'class': [1563, 1570, 1590, 1599, 1609, 1617, 1668, 3556, 3559, 3565, 3571, 3631, 3672, 3769, 3849], '(1-spacing,': [1564, 1591, 1600], 'linker)': [1566], 'JIP1': [1569, 2227, 3630], '(2-spacing,': [1571, 1610, 1627], 'linker).': [1573], 'On': [1574], 'hand,': [1577], 'known': [1578, 1656, 2056, 2471, 2687, 3058, 3384, 3748, 4079], 'ERK1/2': [1579], 'p38': [1581, 1621, 2383], 'binder': [1582], 'belong': [1585], 'greater': [1588, 1597, 1607, 1667], 'MEF2A': [1589, 3558, 3614], 'linker,': [1593, 1602, 1612, 1629], 'end),': [1595, 1604, 1631], 'HePTP': [1598, 3570], 'helical': [1603, 1630, 2446], 'DCC': [1608, 3454, 3564, 3588], 'end).': [1614], 'sixth': [1616], 'interactors': [1622, 2461, 3445], 'theoretically': [1624], 'possible': [1626, 2082], 'combination': [1634, 2171], 'observed': [1638], 'long': [1640], 'reverse': [1641], '(revD)': [1642], '2012),': [1647], 'no': [1649, 3926, 4200, 4222], 'classical': [1650], 'type': [1654, 2971, 3745, 3756], 'up': [1657, 2487], 'date.': [1659], 'Subtypes': [1660], 'variants': [1663], 'within': [1664], 'featured': [1671, 3739, 3992], 'wherever': [1672], 'applicable.': [1673], 'structures': [1679, 2071, 2207], 'complexes.': [1683], 'Dashed': [1684], 'lines': [1685], 'indicate': [1686, 3757, 4160], 'peptide': [1688, 2881, 3022, 4142, 4229], 'usually': [1692], 'visible': [1694], 'structures,': [1698], 'albeit': [1699], 'indispensable': [1700], 'Consensus': [1703], 'subtype': [1707], 'below,': [1710], 'where': [1711, 3181, 4162], 'φU,': [1712], 'φL,': [1713, 2280], 'φA,': [1714, 2281], 'φB': [1716, 2283], 'letters': [1717], 'denote': [1718, 2284, 3746], 'positions': [1719, 1743, 2285], 'filled': [1722, 2289], 'acids—L,': [1726, 2293], 'A,': [1727, 2294], 'B': [1729, 2296], 'refer': [1730, 2297, 3971], 'lower': [1733, 2300], 'pocket,': [1734, 2301], 'pockets': [1736, 2303], 'B,': [1739, 2306], 'respectively—while': [1740, 2307], 'positively': [1745, 1810, 2311], '(Arg': [1747], 'Lys)': [1749], 'letter': [1751], '"x"': [1752, 2317], 'denotes': [1753, 2310, 2318, 3297], 'arbitrary': [1754], 'acids.': [1756], 'Download': [1757, 1759, 2846, 2848, 3339, 3341, 3545, 3547, 4040, 4042], 'figure': [1758, 2847, 3340, 3546, 4041], 'PowerPoint': [1760, 2849, 3342, 3548, 4043], 'Several': [1761], 'previous': [1762], 'attempts': [1763], 'aimed': [1765, 1944], 'predicting': [1767], 'full': [1771], 'using': [1774, 2145, 3196], 'generic': [1776], 'had': [1782, 1855, 2677, 2746, 2778, 2888, 3960], 'established': [1784], 'than': [1786, 3767, 3962, 3995], 'decade': [1788], 'ago': [1789], '(Sharrocks': [1790], '2000).': [1793], 'derived': [1797, 3277], 'observation': [1800], 'almost': [1803, 2684], 'include': [1805], 'least': [1807, 3426, 3910, 3983], 'single': [1809, 1937], 'residue': [1812], '(termed': [1813], 'position:': [1816], 'arginine': [1817], 'lysine)': [1819, 2315], 'series': [1822, 2741], 'alternating': [1824], '(φ': [1827], 'positions:': [1828], 'frequently': [1829], 'leucine),': [1830], 'connected': [1831], '(Dinkel': [1839], 'But': [1843], 'despite': [1844], 'use': [1846, 2864], 'multiple': [1849, 2099, 3773], 'alignments': [1850], 'sophisticated': [1852], 'algorithms,': [1853], 'predictions': [1854], 'success': [1858], 'rates': [1859], 'assessment': [1862], 'predicted': [1864, 2637, 3364], 'hits': [1865, 2606, 3486], 'performed': [1868, 2660, 2824, 3890, 3904], '(Whisenant': [1869], '2010;': [1872], '2012;': [1876, 2253], 'Gordon': [1877], '2013).': [1880, 1918], 'Regarding': [1881], 'network': [1884, 2032], 'discovery,': [1885], 'ERK2': [1886, 1902, 1972, 2475, 3314], 'widely': [1891], 'explored.': [1892], 'For': [1893, 2219, 3999], 'example,': [1894, 2220], 'several': [1895, 3443], 'methods': [1897], 'utilized': [1899, 3207], 'identify': [1901, 1998], 'phosphoproteomics': [1906], '(Kosako': [1907], '2009;': [1910, 2569], 'Carlson': [1911], '2011;': [1914], 'Courcelles': [1915], 'Unfortunately,': [1919], 'pairwise': [1920], 'overlaps': [1921], 'between': [1922, 1939, 2699], 'lists': [1924, 3360, 3702], 'across': [1929, 2365], 'studies': [1930, 1942, 1991], 'around': [1932], '~10%),': [1933], 'overlap': [1938], 'five': [1940], 'find': [1946, 2725], 'ERK2-phosphorylated': [1947], '(Courcelles': [1949], '2013),': [1952], 'suggesting': [1953], 'great': [1954], 'dependence': [1955], 'conditions': [1959], 'used.': [1960], 'It': [1961], 'noted': [1963], 'D-motif-like': [1965], 'enriched': [1968], 'detected': [1971, 3190], '(Carlson': [1974], '2011),': [1977], 'yet': [1978], 'detection': [1979], 'verification': [1981], 'association': [1985], 'performed.': [1988], 'In': [1989, 2060, 2125, 2521, 2654, 3343, 3436, 3820, 3900, 4092], 'addition,': [1990, 2655, 3821], 'high-throughput': [1995], 'partners': [1999], '(Chen': [2002], '2014)': [2005], 'p38α': [2007, 3316], '(Bandyopadhyay': [2008], '2010)': [2011], 'resulted': [2017], 'hits.': [2022], 'Thus,': [2023], 'likely': [2026], 'interaction-based': [2030], 'could': [2034, 2270, 2872, 3121, 4109, 4165], 'greatly': [2035], 'benefit': [2036], 'approach,': [2041], 'takes': [2043, 3183], 'account—and': [2045], 'possibly': [2046], 'capitalizes': [2047], 'on—specific': [2048], 'biochemical': [2049], 'biophysical': [2051], 'knowledge': [2052], 'already': [2053], 'available': [2054, 2835], 'MAPK–partner': [2057, 2068], 'interactions.': [2059, 3034], 'recent': [2061], 'years,': [2062], 'determined': [2067], 'increased': [2072], 'considerably': [2073], 'development': [2079], 'made': [2080], 'amend': [2084], 'definition': [2086, 3833, 3850, 3864], 'underlying': [2089], 'became': [2094], 'clear': [2095], 'encompass': [2098], 'similarly': [2102], 'built,': [2103], '(similar': [2109], 'SH3-': [2111], 'PDZ-domain-binding': [2113], 'sequences,': [2114], 'example)': [2116], '(Lim': [2117], '1994;': [2120], 'Tonikian': [2121], '2008).': [2124], 'current': [2127], 'study,': [2128], 'show': [2130, 3287, 3519, 4045], 'building': [2133], 'strategy': [2135], 'handle': [2138], 'conformational': [2140, 2403], 'diversity': [2141], 'binding,': [2143], 'structural': [2146, 2858, 2882, 2929], 'compatibility': [2147, 2930], 'specific': [2149, 3140, 3238], 'topography': [2152], 'criterion': [2156], 'prediction,': [2158], 'dramatically': [2166], 'improved.': [2167], 'techniques': [2175], '(1–20': [2181, 3031], 'μM)': [2182, 3032], 'unique,': [2186], 'molecular-level': [2187], 'insight': [2188], 'evolution': [2193], 'MAPK-based': [2195], 'networks.': [2197], 'Results': [2198, 3515], 'Structure-guided': [2199], 'prediction': [2200], 'MAPK–D-peptide': [2205], 'revealed': [2208], '1).': [2218], 'JNK-binding': [2224, 3234], 'JNK-regulated': [2231], 'transcription': [2232], 'factor': [2233], 'differently': [2241], '1A': [2243], 'B)': [2245], '(Heo': [2246], '2004;': [2249], 'Laughlin': [2254], 'Similarly,': [2258], 'ERK-': [2259], 'p38-binding': [2261], 'distinct;': [2267], 'nonetheless,': [2268], 'described': [2272], 'loosely': [2276], 'defined': [2277, 3403], '[θ1,2-x(0-5)-φL-x(1,2)-φA-x-φB;': [2279], '(arginine': [2313], 'any': [2319], 'acid].': [2321], 'rules': [2324], 'much': [2326], 'stricter': [2327], 'compatible': [2332], 'mode.': [2342], 'Interestingly,': [2343, 2443], 'conserved': [2351, 2364], 'yeast': [2353, 2463], 'well': [2363, 3082], 'eukaryotes': [2367], '(Reményi': [2368], '2005;': [2371], 'Grewal': [2372], 'Because': [2376], 'wider': [2385], 'JNK,': [2390], 'former': [2399], 'have': [2401, 3406], 'larger': [2402], 'freedom': [2404], '1C)': [2406], 'classified': [2414, 3938], 'MEF2A-': [2416], 'DCC-type': [2418, 3578], 'named': [2420], 'after': [2421, 2680], 'first': [2428, 2547, 2998, 4190], 'identified.': [2429], 'Some': [2430], 'intervening': [2434], 'exists': [2437], '(HePTP)': [2438], '(Zhou': [2439], 'typical': [2445], 'N-terminus': [2450], 'HePTP-type': [2452], 'some': [2459, 3394], '(Ste7)': [2464], 'high': [2477, 3483], '(Fernandes': [2479], '2007).': [2482], 'hypothetical': [2489], 'subclass': [2490], 'Ste7-type': [2492], 'hitherto': [2494], 'unknown': [2495], 'humans': [2497], '1D).': [2499], 'Simple': [2500], 'pattern': [2501], 'matching': [2502], 'normally': [2505], 'produces': [2506], 'false': [2511, 2529], 'positives,': [2512], 'motif-matching': [2514, 2731], 'occur': [2517], 'simply': [2518], 'chance.': [2520], 'order': [2522, 2579, 2767, 3390], 'drastically': [2524], 'reduce': [2525], 'hits,': [2530], 'filtering': [2534], 'procedure': [2535, 2575], 'implemented': [2537], 'search': [2539], '2).': [2545], 'step': [2548, 2732, 2993], 'screen': [2551], 'intrinsic': [2557], 'disorder': [2558], 'propensity': [2561], 'disorder-to-order': [2563], 'transition': [2564], '(ANCHOR)': [2565], '(Dosztányi': [2566], '2009).': [2573], 'eliminate': [2581], 'those': [2582, 3857], 'would': [2587], 'either': [2588], 'buried': [2590], 'folded': [2592], 'permanently': [2595], 'locked': [2596], 'unfavorable': [2599], 'conformation.': [2600], 'Importantly,': [2601], 'removed': [2604], 'initial': [2605, 2959], 'inappropriate': [2609], 'composition,': [2612], 'being': [2614, 2948, 4191], 'able': [2615, 3440], 'surface.': [2626], 'Motifs': [2627, 2634, 3841], 'then': [2629], 'filtered': [2630], 'accessibility:': [2633], 'lie': [2639], 'extracellular': [2641], 'kinase-inaccessible': [2647], 'compartments': [2648], 'ER,': [2650], 'Golgi)': [2651], 'discarded.': [2653], 'check': [2658], 'against': [2661, 3252, 3533, 4074], 'structured': [2662], 'Pfam': [2663, 2764], 'domains.': [2664], 'remove': [2669], 'spurious': [2671], 'ordered': [2674], 'retained': [2679], 'ANCHOR': [2681, 2751, 2775], 'filtering.': [2682], 'Since': [2683], 'passed': [2689], 'filters': [2691], '(45': [2692], 'out': [2693], '47,': [2695], 'enrichment': [2697], 'ratios': [2698], '4.1': [2700], '6.6': [2702], 'depending': [2703], 'type),': [2706], 'concluded': [2708], 'dataset': [2711], 'sufficient': [2714], 'quality': [2715], 'further': [2717], 'testing.': [2718], '2.': [2720], 'Motif': [2721], 'finding': [2722], 'work': [2723], 'flowTo': [2724], 'primary': [2730], '(on': [2733], 'UniProt': [2734], 'KB': [2735], 'sequences)': [2736], 'followed': [2738], 'filters.': [2743], 'Valid': [2744], 'pass': [2748], 'filter,': [2752, 2765], 'localization': [2754], 'filter': [2755], '(combined': [2756], 'SignalP': [2758], 'Phobius)': [2760], 'scored': [2770], 'FoldX': [2772, 2794], 'homology': [2773], 'models.': [2774, 3455], '(middle': [2776], 'panel)': [2777], 'role': [2782], 'selecting': [2784], 'potentially': [2788], 'act': [2789], 'gave': [2795], 'motif-specific': [2796], 'energy': [2798, 2902, 2907, 2937, 3366], 'estimates': [2799, 2938], '(see': [2800, 3541, 3834, 4154], 'data).': [2802], 'Predicted': [2803], 'subsequently': [2806], 'tested': [2807, 3246, 3301, 3705, 3967], 'fragments': [2810, 3226], '(in': [2812], 'selected': [2813, 3357], 'cases)': [2814], 'full-length': [2816, 2976], 'Finally,': [2818], 'automated': [2820], 'evolutionary': [2821, 3955], 'give': [2826], 'information': [2827], 'conservation': [2830], 'trends.': [2831], 'data': [2833], 'online': [2836], 'figure.': [2839, 3512, 3781, 4118], '2': [2844], '[msb156269-sup-0007-SDataFig2.xls]': [2845], 'coherent': [2857], 'us': [2861], 'make': [2863], 'structure-based': [2866], 'scoring.': [2867], 'occurrence': [2871], 'unambiguously': [2875], 'matched': [2876], 'its': [2878, 3846], 'corresponding': [2879, 3313], 'model,': [2883, 3461], 'FoldX,': [2886], 'validated': [2890], 'complexes,': [2893], 'estimate': [2895], 'change': [2897], 'respect': [2904], 'resolved': [2911], '(Appendix': [2913], 'Table': [2914, 3549], 'S1)': [2915], '(Schymkowitz': [2916], '2005).': [2919], 'allowed': [2921], 'scoring': [2923], 'according': [2926, 3791, 3816], 'FoldX-derived': [2935], 'guide': [2944], 'when': [2945], 'chosen': [2949], 'later': [2951], 'screening.': [2953], 'Experimental': [2954], 'screening': [2955], 'After': [2956], 'completion': [2957], 'lists,': [2960], 'chose': [2962], 'candidate': [2966], 'test.': [2973], 'Expression': [2974], 'size': [2981], '(>': [2982], '1,000': [2983], 'acids)': [2985], 'recombinant': [2987, 3016, 3110], 'systems': [2988], 'limiting': [2992], 'validation;': [2996], 'therefore,': [2997], 'opted': [3000], 'fragment-based': [3003], 'approach.': [3004], 'Former': [3005], 'experiments': [3006, 3788, 3874], 'showed': [3007], 'assays': [3011], '(such': [3012], 'pull-downs': [3014], 'D-motif-containing': [3017, 3059, 3527, 3798], 'immobilized': [3020, 3176], 'solid-phase': [3021, 3050, 3179], 'arrays)': [3023], 'lack': [3024], 'robustness': [3026], 'reliably': [3028], 'developed': [3037], 'assay': [3040], 'substrate': [3045, 3075, 3106, 3218], 'enhancement': [3047, 3170], 'support': [3051, 3180], '3A).': [3053], 'majority': [3056], 'substrates,': [3063], 'adequately': [3065], 'captures': [3066], 'original': [3068], 'function': [3069], 'An': [3073], 'artificial': [3074, 3205], 'constructed': [3077], 'containing': [3078], 'Thr71': [3085], 'ATF2,': [3089], 'well-known': [3093], '(Livingstone': [3097], '1995)': [3100], '3B).': [3102], 'linkers': [3104], 'identical,': [3113], '"docking': [3115], 'efficiency"': [3116], 'directly': [3123, 3356], 'other.': [3127], 'Phosphorylation': [3128], 'reporter': [3131], 'solely': [3132], 'depended': [3133], 'presence': [3136, 4055], 'absence': [3138], 'without': [3151], '3C': [3156], 'D).': [3158], '3.': [3160], 'Dot-blot': [3161], 'arrays': [3162, 3319, 3324, 3712], 'principle': [3166], 'dot-blot': [3171, 3210, 3230, 3260, 3517, 3711, 3787, 3873], 'arrays.': [3172, 3211], 'constructs': [3174, 3213, 3525, 3980], 'onto': [3177], 'place.': [3184], 'Afterward,': [3185], 'phosphorylated': [3187], 'epitopes': [3188], 'standard': [3192, 3288], 'Western': [3193], 'blot': [3194], 'procedures': [3195], 'phosphorylation-sensitive': [3198], 'antibody.': [3199], 'schematic': [3201], 'All': [3212, 3262], 'share': [3214], 'tags,': [3217], 'sites,': [3219], 'linkers:': [3221], 'Only': [3222, 3942], 'motif-containing': [3225], 'differ.': [3227], 'sample': [3229, 3259], 'array': [3231, 3239], 'detecting': [3233], '48': [3241, 3317], '70': [3244, 3322, 3349], 'total,': [3248], 'incubated': [3251], 'activated': [3253], 'JNK1.': [3254], 'Quantitative': [3255], 'array.': [3261], 'intensities': [3263], 'relative': [3265], '(positive': [3272], 'control),': [3273], 'error': [3274], 'bars': [3275], 'parallel': [3280], 'samples': [3281], 'membrane': [3285], 'deviation': [3289], 'mean': [3292], '(N': [3293], '=': [3294], '3).': [3295], '"+"': [3296, 3970], 'additional,': [3298], 'non-overlapping': [3299, 3964], 'protein.': [3305, 3480], '"m"': [3306], 'refers': [3307, 4027], 'murine': [3309, 4030], '(non-human)': [3310], 'sequence.': [3311], 'Appendix': [3332, 3370, 3504, 3835, 4089, 4156], 'Fig': [3333, 3337, 3371, 3501, 3505, 3543, 3836, 4090, 4157], 'S1': [3334], 'EV1).': [3338], 'final': [3345], 'panels,': [3346], 'included': [3348, 3375], 'constructs:': [3351], '63': [3352], 'ranked': [3361], 'EV1': [3368], 'S1).': [3372, 3544], 'seven': [3377], 'similarity': [3382], 'done': [3388], 'whether': [3393], 'similar': [3396], 'conforming': [3399], 'formerly': [3402], 'patterns': [3405], 'capacity': [3408, 4217], 'Out': [3412], '70,': [3414], 'total': [3416], '52': [3418], 'interact': [3423], 'one': [3427, 3768, 3911, 3996], '(ERK2,': [3432], 'JNK1,': [3433], 'p38α).': [3435], 'particular,': [3437], 'JIP1,': [3449], 'NFAT4,': [3450], 'MKK6,': [3452], 'our': [3458], 'hypothetic': [3459], 'Ste7': [3460], 'hit:': [3467], 'RHDF1': [3471], 'RHDF2': [3479], 'suggest': [3487], 'fact': [3492], 'quite': [3493], 'widespread': [3494], '(Table': [3499], '1,': [3500], 'EV2,': [3502], 'S2).': [3506], 'Click': [3507, 3776, 4113], 'here': [3508, 3777, 4114], 'expand': [3510, 3779, 4116], 'EV1.': [3514], 'experimentsPanels': [3518], 'dot': [3520], 'blots': [3521], '71': [3524], '(70': [3526], '+': [3529], 'negative': [3531], 'control)': [3532, 3896], 'epitope': [3538], 'density': [3539], 'alsoAppendix': [3542], 'Validated': [3551], 'grouped': [3553, 3790, 3815, 4185], 'D-Motif': [3555], 'Greater': [3557, 3563, 3569], '(phosphorylation': [3560, 3566, 3572, 3632, 3673], 'p38α)': [3562], 'ERK2)': [3568, 3574], 'MEF2A-type': [3575], 'MKK6-type': [3576], 'Misc.': [3577], 'Far1-type': [3579], 'Ste7-like': [3580], 'HePTP-like': [3581], 'AAKG2/PRKAG2': [3582], '(28–37)': [3583], 'CCNT2': [3584], '(498–509)': [3585], 'AMPD1': [3586], '(109–120)': [3587], '(1,144–1,155)': [3589], 'CBLB': [3590], '(489–500)': [3591], 'RHDF1/iRhom1': [3592], '(11–24)': [3593], 'ZEP1/HIVEP1': [3594], '(1,422–1,438)': [3595], 'JAZF1': [3596], '(77–86)': [3597], 'GAB3': [3598], '(363–374)': [3599], 'AMPD3': [3600], '(79–90)': [3601], 'CACNA1G': [3602], '(1,030–1,041)': [3603], 'ELMSAN1': [3604], '(601–612)': [3605], 'RHDF2/iRhom2': [3606], '(18–31)': [3607], 'INO80a': [3608, 3610], '(1,318–1,327)': [3609], '(1,316–1,327)': [3611], 'TRERF1': [3612], '(653–664)': [3613], '(268–277)': [3615], 'KSR2': [3616], '(330–341)': [3617], 'GAB1': [3618], '(526–536)': [3619], 'KLF3': [3620], '(88–97)': [3621], 'KMT2C/MLL3a': [3622, 3624], '(1,195–1,206)': [3623], '(1,197–1,206)': [3625], 'RIPK2a': [3626, 3696], '(326–335)': [3627], 'TSHZ3a': [3628, 3698], '(321–330)': [3629], 'JNK1)': [3634, 3675], 'APBA2/MINT2': [3635], '(279–285)': [3636], 'ATF2': [3637], '(164–170)': [3638], 'ATF7': [3639], '(162–168)': [3640], 'APC2': [3641], '(962–968)': [3642], 'BMPR2': [3643], '(753–759)': [3644], 'DOCK5': [3645], '(1,762–1,768)': [3646], 'DOCK7': [3647], '(884–890)': [3648], 'DUSP10/MKP5': [3649], '(18–24)': [3650], 'ELK1': [3651], '(314–320)': [3652], 'IRS1': [3653], '(856–862)': [3654], 'JIP3': [3655], '(203–209)': [3656], 'M3K10/MLK2': [3657], '(876–882)': [3658], 'MADD': [3659], '(809–815)': [3660], 'MCL1': [3661], '(136–142)': [3662], 'MYO9B': [3663], '(1,249–1,255)': [3664], 'PDE4B': [3665], '(72–78)': [3666], 'PRGC1/PPARGC1A': [3667], '(253–259)': [3668], 'SAC2/INSPP5': [3669], '(1,009–1,015)': [3670], 'AKAP6/mAKAP': [3676], '(433–440)': [3677], 'CCSER1': [3678], '(573–580)': [3679], 'DYH12/DNAH12': [3680], '(12–19)': [3681], 'FMN1': [3682], '(672–679)': [3683], 'FHOD3': [3684], '(506–513)': [3685], 'JUND': [3686], '(46–53)': [3687], 'KANK2': [3688], '(244–251)': [3689], 'M3K10/MEKK1': [3690], '(1,077–1,084)': [3691], 'MABP1': [3692], '(1,292–1,299)': [3693], 'NFATC3/NFAT4': [3694], '(145–152)': [3695], '(327–334)': [3697], '(322–329)': [3699], 'table': [3701], 'positive': [3707], '("hits")': [3708], 'shows': [3715], 'commonly': [3718], 'names': [3720, 3753], '(when': [3723], 'necessary,': [3724], 'variants),': [3726], 'together': [3727, 4144], 'position': [3730], 'core': [3733], 'motif—based': [3734], 'reference': [3737], 'isoform': [3738, 4012], 'UniProt.': [3741, 4023], 'Names': [3742], 'bold': [3744, 3854], 'previously': [3747], 'normal': [3755, 3868], 'interactors.': [3759], 'Denotes': [3761], 'appear': [3764], 'under': [3765, 3993], 'satisfy': [3772], 'sequences.': [3775], 'EV2.': [3783], 'Constructs': [3784], 'classAmino': [3794], 'ligated': [3801], 'pAZAD': [3804], 'vector': [3805], 'displayed': [3807, 4132], 'tabulated': [3810, 4135], 'format.': [3811], 'Tested': [3812], 'types.': [3819], 'conformity': [3823], 'loose': [3829], 'tight': [3831, 3847], 'S2)': [3837], 'indicated:': [3840, 3877], 'whose': [3842], 'fits': [3844], 'written': [3852], 'type,': [3855], 'correspond': [3860], 'looser': [3863], 'type.': [3869], 'outcome': [3871], 'regarded': [3881], '"strong': [3884, 3943], 'binder"': [3885], '(unequivocally': [3886], 'positive)': [3887], 'if': [3888, 3902], 'above': [3891, 3918, 4172], 'cutoff': [3893, 3907], '(non-cognate': [3894], 'experiments.': [3899], 'case': [3901], 'below': [3905], 'round': [3912], 'experiments,': [3914], 'still': [3916], 'consistently': [3917], 'level': [3920], 'zero': [3922], '(substrate': [3924], 'D-motif),': [3927], 'considered': [3930, 3946], '"weak': [3932], 'binder".': [3933], 'Otherwise,': [3934], '"non-binder".': [3941], 'binders"': [3944], '"positives"': [3948], 'purpose': [3951], 'analysis.': [3956], '+:': [3957], 'one,': [3963], '(names': [3968], 'with/without': [3969], 'sequences).': [3974], '*:': [3975], 'satisfies': [3981], 'different,': [3985], 'overlapping': [3986], '(thus,': [3989], 'class/subclass).': [3998], 'sake': [4001], 'simplicity,': [4003], 'shown.': [4008], '∼:': [4009], 'NCBI': [4016], 'databases': [4019], 'm:': [4024], 'instead': [4031], '(Kim': [4036], 'To': [4044], 'enhancements': [4049], 'indeed': [4051], 'due': [4052], 'canonical': [4057], 'groove,': [4064, 4100], '16': [4068], 'chemically': [4069], 'synthesized': [4070], 'titrated': [4073], 'fluorescently': [4075], 'labeled': [4076], 'EV3': [4087], 'S3).': [4091, 4158], 'addition': [4093], 'confirming': [4095], 'dissociation': [4102, 4147], 'constant': [4103], '(Kd)': [4104, 4149], 'unlabeled': [4106], 'calculated.': [4112], 'EV3.': [4120], 'Protein–peptide': [4121], 'assaysThe': [4124], 'results': [4125], 'fluorescence': [4127], 'polarization': [4128], '(FP)': [4129], 'titrations': [4130], 'format,': [4136], 'showing': [4137], 'synthetic': [4141], 'constants': [4148], 'obtained': [4150], 'Dashes': [4159], 'cases': [4161], 'curves': [4164], 'fitted': [4168], '(the': [4169], 'Kd': [4170], 'limit': [4174], 'quantitation': [4176], 'assay,': [4179], 'approximately': [4180], '~100': [4181], 'μM).': [4182], 'Peptides': [4183], 'clusters,': [4188], 'strong': [4193, 4213], 'binders': [4195], '(frequently': [4196], 'little': [4198, 4220], 'ERK2/p38α-binding': [4201], 'ability).': [4202], 'second': [4204], 'group': [4205], '(below': [4206], 'magenta': [4208], 'line)': [4209], '(but': [4218], 'toward': [4224], 'JNK1).': [4225], 'Coloring': [4226], 'displays': [4231], 'critical': [4233]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2159056768', 'counts_by_year': [{'year': 2024, 'cited_by_count': 4}, {'year': 2023, 'cited_by_count': 8}, {'year': 2022, 'cited_by_count': 8}, {'year': 2021, 'cited_by_count': 9}, {'year': 2020, 'cited_by_count': 6}, {'year': 2019, 'cited_by_count': 8}, {'year': 2018, 'cited_by_count': 9}, {'year': 2017, 'cited_by_count': 6}, {'year': 2016, 'cited_by_count': 5}], 'updated_date': '2024-12-08T23:37:28.155174', 'created_date': '2016-06-24'}
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