Functional distinctions of yeast Hsp40 (J-protein) chaperones in thermotolerance, prion propagation and prion elimination.

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NIDDK	CELLBIO-12

Authors

• M. REidy
• R. Sharma
• S. Shastry
• B-L. Roberts
• I. Albino-Flores
• S. Wickner
• DC Masison

Abstract

Hsp100 family chaperones of microorganisms and plants cooperate with the Hsp70/Hsp40/NEF chaperone system to resolubilize and reactivate stress-denatured proteins. In yeast this protein disaggregation machinery also promotes propagation of amyloid-based prions by fragmenting prion polymers. How functions of this machinery are regulated to act in different processes is uncertain. We previously showed the E. coli Hsp100 machinery cooperates specifically with the yeast Hsp40 Ydj1 to support yeast thermotolerance and with Sis1 to propagate prions. Here we find these Hsp40s similarly directed specific activities of the yeast Hsp104-based machinery. We show their C-terminal substrate-binding domains determined functional distinctions in these and other processes dependent on chaperone complexes. We find propagation of [URE3] prions was acutely sensitive to alterations in Sis1 activity, and show this sensitivity explains how overexpressing Ydj1 cures cells of [URE3] through competition with Sis1 for interaction with the disaggregation machinery. Our findings support the idea that differences in ways prions respond to various chaperone alterations can be due to differences in their dependence on the disaggregation machinery.

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