Different yeast prions depend differently on functions of yeast Sis1 J-protein Hsp40

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NIDDK	GEN-7

Authors

• C.P. Lin
• B. Roberts
• D.C. Masison

Abstract

From previous data, we have shown that in the yeast Hsp40p, Sis1, deletion or mutation at outside of the conserved J-domain wouldn’t affect the propagation of [PSI+] prions. Here, we systematically evaluate a series of Sis1 mutants to determine Sis1 requirements of [URE3] and [PIN+] prions. In contrast to [PSI+], [URE3] was exquisitely sensitive to alterations of any Sis1 activity and was lost rapidly from cells expressing the mutant proteins in place of Sis1. Some mutants had strong dominant inhibitory effects that depended partially on their ability to dimerize or bind substrates, suggesting they interfere with wild type Sis1 by forming poisoned heterodimers or competing with wild type Sis1 for substrates. [PIN+] was less sensitive to alterations of Sis1 activities than [URE3], but more sensitive than [PSI+]. In line with Sis1 acting as a crucial component of the disaggregating machinery for replicating prions, we present a model incorporated with the spectrum of different prion species and suggest that the differential dependency of these prions on Sis1 is related to the capacity that this machinery is able to fragment the prions.

back to top