Release of linker histone from the nucleosome driven by polyelectrolyte competition with a disordered protein.


Journal

Nature chemistry
ISSN: 1755-4349
Titre abrégé: Nat Chem
Pays: England
ID NLM: 101499734

Informations de publication

Date de publication:
02 2022
Historique:
received: 22 08 2020
accepted: 19 10 2021
pubmed: 8 1 2022
medline: 23 2 2022
entrez: 7 1 2022
Statut: ppublish

Résumé

Highly charged intrinsically disordered proteins are essential regulators of chromatin structure and transcriptional activity. Here we identify a surprising mechanism of molecular competition that relies on the pronounced dynamical disorder present in these polyelectrolytes and their complexes. The highly positively charged human linker histone H1.0 (H1) binds to nucleosomes with ultrahigh affinity, implying residence times incompatible with efficient biological regulation. However, we show that the disordered regions of H1 retain their large-amplitude dynamics when bound to the nucleosome, which enables the highly negatively charged and disordered histone chaperone prothymosin α to efficiently invade the H1-nucleosome complex and displace H1 via a competitive substitution mechanism, vastly accelerating H1 dissociation. By integrating experiments and simulations, we establish a molecular model that rationalizes the remarkable kinetics of this process structurally and dynamically. Given the abundance of polyelectrolyte sequences in the nuclear proteome, this mechanism is likely to be widespread in cellular regulation.

Identifiants

pubmed: 34992286
doi: 10.1038/s41557-021-00839-3
pii: 10.1038/s41557-021-00839-3
doi:

Substances chimiques

Histones 0
Intrinsically Disordered Proteins 0
Nucleosomes 0
Polyelectrolytes 0

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

224-231

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Pétur O Heidarsson (PO)

Department of Biochemistry, University of Zurich, Zurich, Switzerland. pheidarsson@hi.is.
Department of Biochemistry, Science Institute, University of Iceland, Reykjavík, Iceland. pheidarsson@hi.is.

Davide Mercadante (D)

Department of Biochemistry, University of Zurich, Zurich, Switzerland.
School of Chemical Sciences, University of Auckland, Auckland, New Zealand.

Andrea Sottini (A)

Department of Biochemistry, University of Zurich, Zurich, Switzerland.

Daniel Nettels (D)

Department of Biochemistry, University of Zurich, Zurich, Switzerland.

Madeleine B Borgia (MB)

Department of Biochemistry, University of Zurich, Zurich, Switzerland.
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Alessandro Borgia (A)

Department of Biochemistry, University of Zurich, Zurich, Switzerland.
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Sinan Kilic (S)

Institut des Sciences et Ingénierie Chimiques (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.

Beat Fierz (B)

Institut des Sciences et Ingénierie Chimiques (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Robert B Best (RB)

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. robert.best2@nih.gov.

Benjamin Schuler (B)

Department of Biochemistry, University of Zurich, Zurich, Switzerland. schuler@bioc.uzh.ch.
Department of Physics, University of Zurich, Zurich, Switzerland. schuler@bioc.uzh.ch.

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Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
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Humans Yoga Low Back Pain Female Male

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