The molecular basis for cellular function of intrinsically disordered protein regions
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The molecular basis for cellular function of intrinsically disordered protein regions. / Holehouse, Alex S.; Kragelund, Birthe B.
In: Nature Reviews Molecular Cell Biology, Vol. 25, 2024, p. 187–211.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - The molecular basis for cellular function of intrinsically disordered protein regions
AU - Holehouse, Alex S.
AU - Kragelund, Birthe B.
N1 - Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41580-023-00673-0
DO - 10.1038/s41580-023-00673-0
M3 - Review
C2 - 37957331
AN - SCOPUS:85174427792
VL - 25
SP - 187
EP - 211
JO - Nature Reviews. Molecular Cell Biology
JF - Nature Reviews. Molecular Cell Biology
SN - 1471-0072
ER -
ID: 374399936