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The role of conformational flexibility in prion propagation and maintenance for Sup35p

T Scheibel1, S L Lindquist

  • 1Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.

Nature Structural Biology
|October 31, 2001
PubMed

Insights

The Saccharomyces cerevisiae [PSI(+)] factor, Sup35p, relies on structural flexibility for its prion-based inheritance. Altering NM protein structure impacts its conversion to amyloid fibers, crucial for cellular behavior changes.

Area of Science:

  • * Molecular biology
  • * Protein biochemistry
  • * Genetics

Background:

  • * The [PSI(+)] factor in Saccharomyces cerevisiae is a prion, a protein-based genetic element.
  • * It arises from a heritable conformational change in the translation termination factor Sup35p.
  • * The prion-determining region (NM) of Sup35p converts from a soluble state to amyloid fibers, a process accelerated by existing fiber nuclei.

Purpose of the Study:

  • * To investigate the role of structure and structural flexibility in soluble NM.
  • * To understand how environmental factors and mutations affect NM conformational conversion.
  • * To explore the link between NM structural properties and prion inheritance.

Main Methods:

  • * In vitro studies of Sup35p NM domain conformational conversion.
  • * Analysis of the effects of elevated temperatures, chemical chaperones, and mutations on NM structure.
  • * Monitoring the rate of nucleated conformational conversion.

Main Results:

  • * Elevated temperatures, chemical chaperones, and specific mutations alter the structural content of NM.
  • * These changes can inhibit or enhance the rate of nucleated conformational conversion.
  • * The study demonstrates a correlation between NM structural modifications and changes in conversion rates.

Conclusions:

  • * Structural flexibility of the NM domain is critical for heritable, protein-based changes in cellular behavior.
  • * Nucleated conformational conversion of Sup35p serves as a model for amyloidogenesis.
  • * Understanding NM structure-function relationships is key to deciphering prion inheritance mechanisms.

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