A novel multifunctional role for Hsp70 in binding post-translational modifications on client proteins [preprint]
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
PreprintPublication Date
2021-08-25Keywords
Hsp70Ssa1
chaperone
cross-linking
mass spectrometry
posttranslational modifications
interactions
proteomics
Amino Acids, Peptides, and Proteins
Fungi
Molecular Biology
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Hsp70 interactions are critical for cellular viability and the response to stress. Previous attempts to characterize Hsp70 interactions have been limited by their transient nature and inability of current technologies to distinguish direct vs bridged interactions. We report the novel use of cross-linking mass spectrometry (XL-MS) to comprehensively characterize the budding yeast Hsp70 protein interactome. Using this approach, we have gained fundamental new insights into Hsp70 function, including definitive evidence of Hsp70 self-association as well as multi-point interaction with its client proteins. In addition to identifying a novel set of direct Hsp70 interactors which can be used to probe chaperone function in cells, we have also identified a suite of PTM-associated Hsp70 interactions. The majority of these PTMs have not been previously reported and appear to be critical in the regulation of client protein function. These data indicate that one of the mechanisms by which PTMs contribute to protein function is by facilitating interaction with chaperones. Taken together, we propose that XL-MS analysis of chaperone complexes may be used as a unique way to identify biologically-important PTMs on client proteins. In vivo confirmation of Hsp70 dimerization Comprehensive direct interactome of Hsp70 Multi-domain interactions between Hsp70 and client proteins Identification of novel biologically-important client protein PTMsSource
bioRxiv 2021.08.25.457671; doi: https://doi.org/10.1101/2021.08.25.457671. Link to preprint on bioRxiv.
DOI
10.1101/2021.08.25.457671Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29901Notes
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Full author list omitted for brevity. For the full list of authors, see article.
The PDF available for download is Version 2 of this preprint. The complete version history of this preprint is available at https://doi.org/10.1101/2021.08.25.457671.
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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/2021.08.25.457671
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.