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Structure and function of the VCP/p47 complex


EMSL Project ID
51779

Abstract

The VCP AAA+ ATPase is a key component of the ubiquitin-proteasome system and is best characterized for its role in unfolding ubiquitylated proteins prior to their degradation. VCP is also involved in other cellular processes, many of which are mediated through its interactions with the p47 adaptor. Our lab solved the first structure of yeast VCP/p47 (known as Cdc48/Shp1) caught in the act of unfolding a native substrate. We now propose to extend our work to study the human complex, which would establish a structural framework to understand how VCP functions in the context of human health and disease. To achieve this goal, we have optimized our biochemical purifications of VCP/p47 and demonstrate by negative stain TEM that the particles are abundant and monodisperse. However, we are currently lacking access to cryo-EM instrumentation because our Titan Krios/K3 is down for several weeks and a timeline for repair remains uncertain.

Project Details

Start Date
2020-12-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Peter Shen
Institution
University of Utah