Title: Structures Of Remotely Related Interacting Protein Homologues Are Less Divergent Than Non-Interacting Homologues
Abstract:Abstract Background: Homologous proteins could display high structural variations felt due to evolutionary divergence at low sequence identity. This classical inverse relationship between sequence ide...Abstract Background: Homologous proteins could display high structural variations felt due to evolutionary divergence at low sequence identity. This classical inverse relationship between sequence identity and structural similarity, established many years ago, has remained true between homologous proteins of known structure over time. However, large number of heteromeric proteins also exist in the structural data bank, where the interacting subunits belong to the same fold and maintain low sequence identity between themselves. It is not clear if there is any selection pressure to deviate from the inverse sequence-structure relationship for such interacting distant homologues, in comparison to pairs of homologues which are not known to interact. Results: We examined 12,824 fold pairs of interacting homologues of known structure, which includes both heteromers and multi-domain proteins. These were compared with monomeric proteins, resulting 26,082 fold pairs as a dataset of non-interacting homologous systems. Our analysis suggests that interacting homologues retain higher structural similarity than non-interacting homologues at diminishing sequence identity in a statistically significant manner. Conclusion: Interacting homologues are more similar in their 3D structures than non-interacting homologues and has a preference towards symmetric association. There appears to be a structural constraint between remote homologues due to this commitment.Read More