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Cited by 13Heat shock proteins researchProtein Structure and DynamicsAdvanced Proteomics Techniques and Applications

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

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Zhu, Mang, Kuechler, Erich R., Wong, Ryan W.K., Calabrese, Gaetano, Sitarik, Ian M., Rana, Viraj, Stoynov, Nikolay, O’Brien, Edward P., Gsponer, Jörg, Mayor, Thibault·2022·Cell Reports
DOI 10.1016/j.celrep.2022.111096PMC PMC9893312

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Abstract

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.

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Metadata

Authors
Zhu, M., Kuechler, E. R., Wong, R. W. K., Calabrese, G., Sitarik, I. M., Rana, V., Stoynov, N., O’Brien, E. P., Gsponer, J., & Mayor, T.
Affiliations
  • University of British Columbia (CA)
  • Pennsylvania State University (US)
Corresponding author
Mayor, Thibault
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2022-07
Volume
40
Issue
3
Pages
111096
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2022.111096
PMC
PMC9893312
OpenAlex
W4286252602
Cited by
13
References
3
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 5
FWCI
0.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation (MCB-1553291)
  • National Institutes of Health (R35-GM124818)
  • Canadian Institutes of Health Research (PJT 148489)
  • Natural Sciences and Engineering Research Council of Canada (04248)
  • Michael Smith Foundation for Health Research
  • National Institute of Health and Medical Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
protein folding, nascent protein, heat stress, protein misfolding, protein aggregation, chaperone-assisted folding, beta-sheet, protein complexes, proteostasis
MeSH terms
Peptides, Protein Binding, Protein Folding, Molecular Chaperones, Proteome

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