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Pulse Labeling Reveals the Tail End of Protein Folding by Proteome Profiling

36 Pages Posted: 29 Apr 2021 Publication Status: Under Review

See all articles by Mang Zhu

Mang Zhu

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

Erich Kuechler

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

Nikolay Stoynov

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

Joerg Gsponer

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

Thibault Mayor

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

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Abstract

Accurate and efficient folding of nascent protein sequences into their native state requires support from the protein homeostasis network. Herein we probed which newly translated proteins are less thermostable to infer which polypeptides require more time to fold within the proteome. Specifically, we determined which of these proteins were more susceptible to misfolding and aggregation under heat stress using pulse SILAC coupled mass spectrometry. These proteins are abundant, short, and highly structured. Notably these proteins display a tendency to form β-sheet structures, a configuration which typically requires more time for folding, and were enriched for Hsp70/Ssb and TRiC/CCT binding motifs, suggesting a higher demand for chaperone-assisted folding. These polypeptides were also more often components of stable protein complexes in comparison to other proteins. All evidence combined suggests that a specific subset of newly translated proteins requires more time following synthesis to reach a thermostable native state in the cell.

Keywords: Protein folding, heat stress, proteostasis, protein aggregation, proteomics

Suggested Citation

Zhu, Mang and Kuechler, Erich and Stoynov, Nikolay and Gsponer, Joerg and Mayor, Thibault, Pulse Labeling Reveals the Tail End of Protein Folding by Proteome Profiling. Available at SSRN: https://ssrn.com/abstract=3836886 or http://dx.doi.org/10.2139/ssrn.3836886
This version of the paper has not been formally peer reviewed.

Mang Zhu

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

Erich Kuechler

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

Nikolay Stoynov

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

Joerg Gsponer

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

Thibault Mayor (Contact Author)

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

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