Pulse labeling reveals the tail end of protein folding by proteome profiling.

CP: Molecular biology heat stress limited proteolysis misfolding protein aggregation protein folding protein mass spectrometry proteomics proteostasis pulse SILAC translation

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 07 2022
Historique:
received: 12 04 2021
revised: 18 05 2022
accepted: 23 06 2022
entrez: 20 7 2022
pubmed: 21 7 2022
medline: 23 7 2022
Statut: ppublish

Résumé

Accurate and efficient folding of nascent protein sequences into their native states requires support from the protein homeostasis network. Herein we probe which newly translated proteins are thermo-sensitive, making them susceptible to misfolding and aggregation under heat stress using pulse-SILAC mass spectrometry. We find a distinct group of proteins that is highly sensitive to this perturbation when newly synthesized but not once matured. These proteins are abundant and highly structured. Notably, they display a tendency to form β sheet secondary structures, have more complex folding topology, and are enriched for chaperone-binding motifs, suggesting a higher demand for chaperone-assisted folding. These polypeptides are also more often components of stable protein complexes in comparison with other proteins. Combining these findings suggests the existence of a specific subset of proteins in the cell that is particularly vulnerable to misfolding and aggregation following synthesis before reaching the native state.

Identifiants

pubmed: 35858568
pii: S2211-1247(22)00898-1
doi: 10.1016/j.celrep.2022.111096
pmc: PMC9893312
mid: NIHMS1864204
pii:
doi:

Substances chimiques

Molecular Chaperones 0
Peptides 0
Proteome 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

111096

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM124818
Pays : United States
Organisme : CIHR
ID : PJT 148489
Pays : Canada

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Mang Zhu (M)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Erich R Kuechler (ER)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Ryan W K Wong (RWK)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Gaetano Calabrese (G)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Ian M Sitarik (IM)

Department of Chemistry, Penn State University, Pennsylvania, PA 16802, USA.

Viraj Rana (V)

Department of Chemistry, Penn State University, Pennsylvania, PA 16802, USA.

Nikolay Stoynov (N)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Edward P O'Brien (EP)

Department of Chemistry, Penn State University, Pennsylvania, PA 16802, USA.

Jörg Gsponer (J)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Thibault Mayor (T)

Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: mayor@msl.ubc.ca.

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