Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics
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Griffin_Distinct prion.pdf
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Author(s)
Frederick, Kendra K.
Debelouchina, Galia Tzvetanova
Kayatekin, Can
Dorminy, Tea
Jacavone, Angela
Griffin, Robert Guy
Lindquist, Susan
Date Issued
January 2014
Journal
Chemistry & Biology
Publisher
Elsevier
Citation
Frederick, Kendra K., Galia T. Debelouchina, Can Kayatekin, Tea Dorminy, Angela C. Jacavone, Robert G. Griffin, and Susan Lindquist. "Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics." Chemistry & Biology 21:2 (20 February 2014), pp. 295-305.
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Author's final manuscript
Abstract
Yeast prions are self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that produce distinct phenotypes. Using magic-angle spinning nuclear magnetic resonance spectroscopy, we provide a detailed look at the dynamic properties of these forms over a broad range of timescales. We establish that different prion strains have distinct amyloid structures, with many side chains in different chemical environments. Surprisingly, the prion strain with a larger fraction of rigid residues also has a larger fraction of highly mobile residues. Differences in mobility correlate with differences in interaction with the prion-partitioning factor Hsp104 in vivo, perhaps explaining strain-specific differences in inheritance.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Whitehead Institute for Biomedical Research
Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.chembiol.2013.12.013
