A Quantitative Chaperone Interaction Network Reveals the Architecture of Cellular Protein Homeostasis Pathways
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Lindquist_A quantitative.pdf
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Author(s)
Taipale, Mikko
Krykbaeva, Irina
Lin, Zhen-Yuan
Larsen, Brett
Choi, Hyungwon
Gingras, Anne-Claude
Tucker, George Jay
Peng, Jian
Berger, Bonnie A.
Lindquist, Susan
Date Issued
July 2014
Journal
Cell
Publisher
Elsevier
Citation
Taipale, Mikko et al. “A Quantitative Chaperone Interaction Network Reveals the Architecture of Cellular Protein Homeostasis Pathways.” Cell 158.2 (2014): 434–448.
Version
Author's final manuscript
Abstract
Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins (clients). In vivo, chaperones also associate with a large and diverse set of cofactors (cochaperones) that regulate their specificity and function. However, how these cochaperones regulate protein folding and whether they have chaperone-independent biological functions is largely unknown. We combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone-cochaperone-client interaction network in human cells. We uncover hundreds of chaperone clients, delineate their participation in specific cochaperone complexes, and establish a surprisingly distinct network of protein-protein interactions for cochaperones. As a salient example of the power of such analysis, we establish that NUDC family cochaperones specifically associate with structurally related but evolutionarily distinct β-propeller folds. We provide a framework for deciphering the proteostasis network and its regulation in development and disease and expand the use of chaperones as sensors for drug-target engagement.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Mathematics
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2014.05.039
