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The molecular basis for cellular function of intrinsically disordered protein regions

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Holehouse, Alex S., Kragelund, Birthe B.·2024·Nature Reviews Molecular Cell Biology
DOI 10.1038/s41580-023-00673-0
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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. Intrinsically disordered regions of proteins lack a defined 3D structure and exist in a collection of interconverting conformations. Recent work is shedding light on how — through their conformational malleability and adaptability — intrinsically disordered regions extend the repertoire of macromolecular interactions in the cell and contribute to key cellular functions.

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Metadata

Authors
Holehouse, A. S., & Kragelund, B. B.
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2023-11-13
Volume
25
Issue
3
Pages
187-211
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/s41580-023-00673-0
OpenAlex
W4388630765
Cited by
696
References
27
FWCI
17.34
Type
journal article
Language
en
Open access
green
Licence

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