College of Liberal Arts & Sciences

End of the Road: Protein Degradation and the Ubiquitin-Proteasome Pathway

Thursday, December 10, 2015

Thursday, December 10, 2015
1:00 pm, MRB 100C

Dr. Mark Hochstrasser

Chair, Department of Molecular Biophysics & Biochemistry
Eugene Higgins Professor of Molecular Biophysics & Biochemistry
Professor of Molecular, Cellular and Developmental Biology
Yale University

End of the Road: Protein Degradation and the Ubiquitin-Proteasome Pathway

Control of cellular protein levels is exerted through changes to both their synthesis and degradation rates. Examples of highly selective protein degradation include that of cell-cycle regulators, which must be present only transiently in the cell cycle, and proteins that misfold or have been damaged, a type of protein quality control. Most short-lived eukaryotic proteins are degraded by the ubiquitin-proteasome pathway. My talk will focus on the proteasome itself. The proteasome is a large and abundant complex, and I will discuss our recent results on its assembly mechanism. Using a combination of genetics, biochemical reconstitutions, quantitative cross-linking/mass spectrometry, and electron microscopy, we have resolved several key facets of proteasome biogenesis, including a remarkable, large-scale conformational remodeling that drives association of proteasome subcomplexes. Such assembly-coupled conformational switching is reminiscent of virus particle maturation, and may represent a commonly used mechanism to enforce hierarchical assembly in multisubunit complexes.

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