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

Mang Zhu, Erich R. Kuechler, Ryan W.K. Wong, Gaetano Calabrese, Ian M. Sitarik, Viraj Rana, Nikolay Stoynov, Edward P. O'Brien, Jörg Gsponer, Thibault Mayor

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article number111096
JournalCell Reports
Issue number3
StatePublished - Jul 19 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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