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Intrinsically disordered regions: comprehensive evolutionary analysis related to the functional properties

FAHMI Muhamad 立命館大学 DOI:info:doi/10.34382/00014049

2020.12.22

概要

Protein Intrinsically disordered regions (IDRs) are polypeptide segments of proteins which fail to form globular tertiary structure in native condition driven by the bias nature of their amino acids sequence. Their peculiar flexible structures not only complement ordered structure functional repertoire but also provide insight into protein capabilities in forming heterogeneous spatiotemporal structures and promiscuous binding, thereby facilitating protein for mediating various functional processes and acting as a hub. Proteins that are involved in either transcription, cellular regulation and signalling, and chromatin remodelling are commonly enriched with IDRs. Additionally, we reported that these flexible polypeptides may also be found in enzymes such as within those of conserved glycoside hydrolases in eukaryotes, in which they were suggested to act as entropic chains either for regulating the distances or enabling movement between domains. IDRs have distinct evolutionary fashion to ordered structure. Understanding a protein evolution may give insight into protein functions, constraints, and interaction landscapes. Here, comprehensive methods and visualizations for investigating structural order-disorder evolution relative to their functional properties were proposed using combination of phylogenetic analysis, IDRs prediction, and evolutionary rate calculation, complemented with other essential information related to their functional properties. CIP/KIP proteins and Rett syndrome-related proteins were used as our models of studies. The results showed that IDRs that act as entropic chains commonly have persistent disordered structures but tend to evolve rapidly. Other functional modules which function by binding generally have lower rate of amino acid substitution and conserved disordered structures, however, some regions within those functional modules were markedly showed several conformational order-disorder transitions and fast rate of amino acid substitutions. These were suggested as of important alterable regions for adapting the binding affinities with their multiple partners along with evolution. Our methods were suggested to be helpful to visualize the evolutionary process of IDRs comprehensively.

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参考文献

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