Abstract
Intrinsically disordered protein regions exist in a collection of dynamic interconverting conformations that lack a stable 3D structure. These regions are structurally heterogeneous, ubiquitous and found across all kingdoms of life. Despite the absence of a defined 3D structure, disordered regions are essential for cellular processes ranging from transcriptional control and cell signalling to subcellular organization. Through their conformational malleability and adaptability, disordered regions extend the repertoire of macromolecular interactions and are readily tunable by their structural and chemical context, making them ideal responders to regulatory cues. Recent work has led to major advances in understanding the link between protein sequence and conformational behaviour in disordered regions, yet the link between sequence and molecular function is less well defined. Here we consider the biochemical and biophysical foundations that underlie how and why disordered regions can engage in productive cellular functions, provide examples of emerging concepts and discuss how protein disorder contributes to intracellular information processing and regulation of cellular function.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Reviews Molecular Cell Biology |
| Vol/bind | 25 |
| Sider (fra-til) | 187–211 |
| Antal sider | 25 |
| ISSN | 1471-0072 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:The authors thank R. Pappu for discussions in the initial phase of writing; G. Daughdrill, A. Flynn, J. Forman-Kay, P. Jemth, A. Moses, J.G. Olsen, R. Pappu, B. Schuler, K. Skriver and S. Sukenik for valuable comments and suggestions; and S. Boeynaems for original microscopy images in Fig. . This work was supported by the Novo Nordisk Foundation challenge grant REPIN, rethinking protein interactions (NNF18OC0033926 to B.B.K.), by the Danish Research Councils (9040-00164B to B.B.K.), by the United States National Science Foundation (NSF) (NSF 2128068 to A.S.H.), by the US NIH (DP2 CA290639-01 to A.S.H.) and by the Human Frontiers in Science Program (RGP0015/2022 to A.S.H.).
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