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NIH Research Festival

September 16 – 18, 2015

Yeast Prions and Heat Shock Proteins

Wednesday, September 16, 2015 – Poster Session I
3:30 – 5:00 p.m.

FAES Terrace

NIDDK

MOLBIO-24

Authors

  • DC Masison

Abstract

Protein chaperones contribute to a protein quality control system that protects proteome integrity. They help proteins adopt and maintain native conformations and facilitate many vital cellular processes. Many disorders result from dysfunction of this machinery or if protein misfolding bypasses this protection. Yeast prions are amyloid aggregates of misfolded proteins that must grow and replicate in order to be maintained in expanding populations. Prion replication requires fragmentation by the Hsp104/Hsp70/Hsp40 protein disaggregation machinery, whose cellular role is to resolubilize proteins from aggregates. Prions differ in their reliance on this machinery so they provide useful tools for studying various aspects of chaperone functions. For example, [URE3] prions, but not [PSI+] prions, are eliminated by elevating the Hsp40 chaperone Ydj1, and [URE3] is much more dependent than [PSI+] on the Hsp40 Sis1. Exploiting these differences, we showed that Ydj1 eliminates [URE3] by competing with Sis1 for interaction with the Hsp70 component of the disaggregation machinery, and that Ydj1 and Sis1 direct and specify activities of this machinery in distinct processes. We also show Ydj1 specifies activity of Hsp90 machinery. Thus, subtle changes in the chaperone landscape beyond detection in other ways can be monitored and evaluated through overt changes in prion phenotypes. Our work provides insight into cooperativity among components of various chaperone machines and the important functional distinctions of nearly identical chaperone isoforms. We highlight our recent findings that demonstrate the power and utility of the yeast prion system for studying functions, specificities and cooperation of chaperone machinery components.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Friday, March 26, 2021

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    • General Schedule of Events
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    • Special Wednesday Events
    • Vendor Exhibit Information
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    • NIH Early–Career Investigator Lectures
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