Comprehensive characterization of the Hsp70 interactome reveals novel client proteins and interactions mediated by posttranslational modifications
Year: 2022
Type: article
Abstract: 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 the inability of current technologies to distinguish direct versus bridged interactions. We report the novel use of cross-linking mass spectrometry (XL-MS) to comprehensively characterize the Saccharomyces cerevisiae (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 multipoint interaction with its client proteins. In addition to identifying a novel set of direct Hsp70 interactors that can be used to probe chaperone function in cells, we have also identified a suite of posttranslational modification (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.
Source: PLoS Biology
Institutions: University of North Carolina at Charlotte, Johns Hopkins University, Johns Hopkins Medicine, University of Oklahoma, Northwestern University, Queen Mary University of London, Goucher College, University of Massachusetts Chan Medical School, Institute of Medical Science, The University of Tokyo, The University of Tokyo, National University of Singapore, Mechanobiology Institute
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,300
Awards: Novel regulation mechanisms of stress responsive pathway by osmotic enhancement of phosphorylation, Understanding the reciprocal regulation between Hsp70 and the DNA damage response, G1727514490, Understanding ER chaperone-mediated RNR regulation, G4160182230, G416069392, G4961690716, Yeast Pheromone Signal Transduction, G822033771, G8614065982
OpenAlex ID: W4307002203