Home > Seminar Announcements, Uncategorized > “Modulating conformation and dynamics to interrogate cellular ubiquitin-deubiquitinase signaling”4:00 p.m. 1005 GBSF Auditorium

“Modulating conformation and dynamics to interrogate cellular ubiquitin-deubiquitinase signaling”4:00 p.m. 1005 GBSF Auditorium

The Genome Center & Structural Biology Focus Group Presents:
Dr. Jacob Corn
Genentech
Early Discovery
“Modulating conformation and dynamics to interrogate
cellular ubiquitin-deubiquitinase signaling”
Ubiquitin is a highly conserved eukaryotic protein that interacts with a diverse set of
partners to act as a cellular signaling hub. Intriguingly, ubiquitin has recently been
shown to be conformationally flexible, is postulated to underlie its multifaceted
recognition. Using computational and library-based means, we interrogate core
mutations of human ubiquitin that modulate its conformational dynamics and find that
human deubiquitinases involved in tumorigenesis are sensitive to ubiquitin’s
conformational state. Using this insight, we engineer new states of ubiquitin that act as
high-affinity deubiquitinase (DUB) probes to inhibit DUB activity in human cells. We
also find that certain DUBs are exquisitely sensitive to the rate with which ubiquitin
switches between states, and show that strict maintenance of the kinetics of ubiquitin’s
motion is necessary for the survival of eukaryotic cells. These results reveal the key
role protein motion plays in a major disease-associated signaling network, and for the
first time demonstrate the importance of “invisible” conformational dynamics in vivo.

Wednesday, November 14th, 2012
4:00 p.m.
1005 GBSF Auditorium
Cookies & Coffee will be provided before the seminar
Faculty Host: Justin Siegel (jbsiegel@ucdavis.edu)
(If you wish an appointment with the invited speaker, please contact the host.)

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