Kylie Walters, Senior Investigator at the NIH NCI Center for Cancer Research's Center for Structural Biology, will deliver a seminar entitled, "Outskirts of the proteasome: substrate receptors and beyond." Hosted by Nate Traaseth.
For more information about Kylie Walters, click here.
Zoom Link: https://nyu.zoom.us/j/96275679242?pwd=ZEV3eU1KbTdCWDNtZUFDMTFuUGJnUT09
Abstract: The 26S proteasome performs regulated protein degradation in eukaryotes. It contains a hollow 20S catalytic core particle (CP), where proteolysis occurs, capped at either end by a 19S regulatory particle (RP), which recognizes and processes ubiquitinated substrates. Receptor sites for ubiquitin or the ubiquitin fold of shuttle factors are scattered throughout the RP and contributed by Rpn1, Rpn10 and Rpn13. We used NMR to resolve how each of these substrate receptors binds ubiquitin chains. Although each interacts with ubiquitin by a distinct structural fold, these receptors share a commonality of binding to ubiquitin chains dynamically. We propose that this dynamic binding to ubiquitin chains is advantageous for the proteasome in capturing ubiquitinated substrates. Deubiquitinating enzymes Usp14 and UCHL5 bind to the proteasome by interaction with Rpn1 and Rpn13 respectively, coupling ubiquitin chain recognition with hydrolysis. In our recent studies, we found a new domain in Rpn10 that is intrinsically disordered but adopts a helical structure to bind E3 ligase UBE3A/E6AP. This talk focuses on these many interactions at the proteasome and their therapeutic potential.