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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Prof. Jason Gestwicki, University of Michigan
Strategies for Targeting Protein-Protein Interactions in the Heat Shock Protein 70 (Hsp70) Complex
School Colloquia
Heat shock protein 70 (Hsp70) is a molecular chaperone that plays critical roles in protein folding and quality control. In these tasks, Hsp70 is assisted by co-chaperones, including J proteins and nucleotide exchange factors, which associate with Hsp70 and help guide its activities. To better understand Hsp70âs cellular roles, our strategy is to identify drug-like small molecules that control the interactions between Hsp70 and its critical co-chaperones. More specifically, we have been exploring a âgray boxâ strategy in which defined Hsp70 complexes are re-constituted in vitro and their emergent activities are used to design chemical screening campaigns. Using this approach, we have screened >155,000 diverse compounds against a number of distinct Hsp70 complexes and identified candidates that interrupt protein-protein interactions with co-chaperones. We have shown that these compounds reduce the levels of some misfolded proteins, such as tau and huntingtin, in cell models. These results suggest that formation of specific Hsp70 complexes controls the fate of some misfolded proteins in disease. Using these chemical probes and additional screening efforts, our long-term goal is to understand how Hsp70âs substrates are selected and how multi-chaperone complexes guide triage decisions.
For more information contact Prof. Raquel Lieberman (404-385-3663).
