PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
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id="title" class="nomar"Structural Basis of Protein Homeostasis

This biological project is composed of investigators from University of California, San Francisco/HHMI and Stanford University, and is partnered with the PSI High-Throughput Structure Determination center NESG.


Consortia Investigators

Peter Walter, Principal Investigator

David Agard

Jonathan Weissman

Judith Frydman


Research Description:

An elaborate network of protein quality control machines facilitates folding of newly made proteins and allows recognition and disposal of terminally misfolded forms. A common theme to this machinery is the ability to recognize unfolded or non-native regions within proteins, either to facilitate their subsequent folding-refolding or degradation, or to signal adaptive responses aimed at restoring the balance between supply and demand in protein folding capacity. Despite its critical importance for physiology and disease, the mechanism by which these machines recognize their substrates remains largely unknown.


We propose to bridge this gap by focusing on physiologically critical systems that cover a range of molecular features but share the need of having to balance specificity and plasticity in molecular recognition. In particular, we focus on cytosolic chaperone substrate recognition (Hsp70, Hsp90, and TRIC chaperones) and the recognition of unfolded proteins in the lumen of the endoplasmic reticulum (ER) for degradation via ER-associated degradation (ERAD) and for signaling via the unfolded protein response (UPR). Our goal is to obtain structural insights into the mechanism by which unfolded and nonnative states are recognized by the cytosolic (Hsp70, Hsp90, TRiC chaperones) and ER (UPR and ERAD pathways) protein homeostasis machineries.


Key publications

New partnership - Coming soon


Structures, Targets, Publications and Technologies

New Partnership - Coming soon

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health