Mechanisms of Macromolecular Interactions Mediated by Protein Intrinsic Disorder

• Published in: Molecules and cells Vol. 43; no. 11; pp. 899 - 908
• Main Authors: Hong, Sunghyun, Choi, Sangmin, Kim, Ryeonghyeon, Koh, Junseock
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.11.2020; 한국분자세포생물학회
• Subjects: Humans; Intrinsically Disordered Proteins - metabolism; Macromolecular Substances - metabolism; Minireview; Signal Transduction; 생물학; multivalent binding; intrinsically disordered proteins or regions; dynamic binding; coupled folding and binding; macromolecular complex; allostery
• ISSN: 1016-8478; 0219-1032; 0219-1032
• DOI: 10.14348/molcells.2020.0186

Intrinsically disordered proteins or regions (IDPs or IDRs) are widespread in the eukaryotic proteome. Although lacking stable three-dimensional structures in the free forms, IDRs perform critical functions in various cellular processes. Accordingly, mutations and altered expression of IDRs are associated with many pathological conditions. Hence, it is of great importance to understand at the molecular level how IDRs interact with their binding partners. In particular, discovering the unique interaction features of IDRs originating from their dynamic nature may reveal uncharted regulatory mechanisms of specific biological processes. Here we discuss the mechanisms of the macromolecular interactions mediated by IDRs and present the relevant cellular processes including transcription, cell cycle progression, signaling, and nucleocytoplasmic transport. Of special interest is the multivalent binding nature of IDRs driving assembly of multicomponent macromolecular complexes. Integrating the previous theoretical and experimental investigations, we suggest that such IDR-driven multiprotein complexes can function as versatile allosteric switches to process diverse cellular signals. Finally, we discuss the future challenges and potential medical applications of the IDR research.