Research shows that the function of intrinsically disordered regions within proteins relies on both linear sequence motifs and broader chemical context, allowing evolution to preserve function without strict sequence conservation. Motifs and contextual chemistry jointly determine activity, with chemistry able to compensate for a loss of motifs.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Cermakova, K. & Hodges, H. C. Trends Biochem. Sci. 48, 477–490 (2023).
Langstein-Skora, I. et al. Nat. Cell Biol. https://doi.org/10.1038/s41556-025-01867-8 (2026).
Holehouse, A. S. & Kragelund, B. B. Nat. Rev. Mol. Cell Biol. 25, 187–211 (2024).
Ruff, K. M. et al. Preprint at bioRxiv https://doi.org/10.1101/2025.02.27.640591 (2025).
Zarin, T. et al. eLife 8, e46883 (2019).
Pritišanac, I. et al. Preprint at bioRxiv https://doi.org/10.1101/2024.03.15.585291 (2024).
Zarin, T. et al. eLife 10, e60220 (2021).
Beh, L. Y., Colwell, L. J. & Francis, N. J. Proc. Natl Acad. Sci. USA 109, E1063–E1071 (2012).
Park, S. O. et al. PLoS Biol. 23, e3003396 (2025).
Tsang, B., Pritišanac, I., Scherer, S. W., Moses, A. M. & Forman-Kay, J. D. Cell 183, 1742–1756 (2020).
Alamdari, S. et al. Preprint at bioRxiv https://doi.org/10.1101/2023.09.11.556673 (2024).
Pesce, F. et al. Sci. Adv. 10, eadm9926 (2024).
Wu, K. et al. Science 389, eadr8063 (2025).
Ginell, G. M. et al. Science 388, eadq8381 (2025).
Zhang, J. et al. Science 390, eadt1630 (2025).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Xiao, YX., Moses, A.M. Motifs and chemistry dictate the role of intrinsically disordered regions. Nat Cell Biol 28, 214–216 (2026). https://doi.org/10.1038/s41556-025-01830-7
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41556-025-01830-7
