Events Calendar

USC PSOC Monthly Seminar Series

Speaker: Andreas Matouschek, Ph.D., Northwestern University

Talk Title: How the Proteasome Picks its Substrates for Degradation

Abstract: The proteasome controls the concentrations of most proteins in the cytosol and nucleus of eukaryotic cells. The degradation signal or degron that targets proteins for proteolysis has two components, a proteasome binding tag, usually a poly-ubiquitin chain, and an initiation site in the form of an unstructured region in the substrate. The two degron components can function in trans when separated onto two different polypeptide chains so that a ubiquitinated adaptor can target a binding partner for proteolysis. Surprisingly, the initiation region contributes significantly to the specificity of Ubiquitin-Proteasome System. The length, location and amino acid sequence of initiation sites all affect whether a protein can be degraded or not. We define these rules in model systems and show how they apply to natural proteins. Once degradation has initiated, the proteasome normally digests its substrates processively to avoid the formation of fragments with undesirable activities. Interestingly, there are a few instances where this processivity breaks down and the proteasome generates partially degraded proteins. The partial degradation is caused by stop signals in the substrate proteins and we propose that this mechanism can explain steps in some signaling pathways and may involved in some neurodegenerative diseases.


Biography: Andreas Matouschek is a biologist at Northwestern University, where he is professor of biochemistry, molecular biology, and cell biology in the Weinberg College of Arts and Sciences. His graduate work with Alan Fersht resulted in the seminal application of phi-value analysis to the study of barnase, a bacterial RNAse used in many protein folding studies.Development of phi value analysis in combination with extensive protein engineering enabled an understanding of the kinetic intermediates during protein folding of barnase. In subsequent postdoctoral work at the University of Basel, he applied the protein engineering approach to studying unfolding of proteins as they pass through mitochondrial translocons.

Matouschek currently studies the proteasome, the degradation machinery of eukaryotic cells, and the mechanisms by which the proteasome is able to unfold and translocate proteins.

Host: USC Physical Sciences in Oncology Center

Location: CSC Harkness Auditorium #250

Audiences: Everyone Is Invited

Contact: Yvonne Suarez