Yanxin Liu, UCSF

Yanxin Liu, UCSF

Special Seminar

Event Date/Location

February 26, 2020 -
4:00 pm to 5:00 pm
Schultz Laboratory 107

Speaker

  • Dr. Yanxin Liu

    UCSF

Topic

Molecular mechanism of the Hsp90 chaperone machinery: co-chaperone regulation and client protein maturation

Heat Shock Protein 90 (Hsp90) is a ubiquitous molecular chaperone that facilitates the folding and maturation of hundreds of “client” proteins, highly enriched for signaling and regulatory processes. Client maturation is assisted by an array of co-chaperones that sequentially interact with Hsp90. Despite their importance, how co-chaperones function is largely unknown. Using cryo-EM, I determined atomic resolution structures for Hsp90 in complex with the ATPase-accelerating co-chaperone Aha1. The structures revealed that Aha1 functions as a conformational activator that catalyzes the Hsp90 cycle by breaking the barriers between 6 distinct and sequentially stabilized states. To dissect the mechanism of client maturation, I established the human succinate dehydrogenase B (SdhB) from respiratory complex II as the first mitochondrial Hsp90 (Trap1) client protein amenable to detailed biochemical and structural investigation. My cryo-EM structure of Trap1:SdhB complex elucidated the interplay between Hsp90 and a partially unfolded SdhB, demonstrating a highly conserved client interaction mechanism that transcends the need for co-chaperones.

Audience

Free and open to the university community and the public.

Host

Fred Hughson, Department of Molecular Biology