Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics

Kendra K. Frederick, Galia T. Debelouchina, Can Kayatekin, Tea Dorminy, Angela C. Jacavone, Robert G. Griffin, Susan Lindquist

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)295-305
Number of pages11
JournalChemistry and Biology
Volume21
Issue number2
DOIs
StatePublished - Feb 20 2014

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Prions
Amyloid
Binding Sites
Phenotype
Magic angle spinning
Yeast
Nuclear magnetic resonance spectroscopy
Conformations
Magnetic Resonance Spectroscopy
Yeasts
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Frederick, K. K., Debelouchina, G. T., Kayatekin, C., Dorminy, T., Jacavone, A. C., Griffin, R. G., & Lindquist, S. (2014). Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics. Chemistry and Biology, 21(2), 295-305. https://doi.org/10.1016/j.chembiol.2013.12.013

Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics. / Frederick, Kendra K.; Debelouchina, Galia T.; Kayatekin, Can; Dorminy, Tea; Jacavone, Angela C.; Griffin, Robert G.; Lindquist, Susan.

In: Chemistry and Biology, Vol. 21, No. 2, 20.02.2014, p. 295-305.

Research output: Contribution to journalArticle

Frederick, KK, Debelouchina, GT, Kayatekin, C, Dorminy, T, Jacavone, AC, Griffin, RG & Lindquist, S 2014, 'Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics', Chemistry and Biology, vol. 21, no. 2, pp. 295-305. https://doi.org/10.1016/j.chembiol.2013.12.013
Frederick, Kendra K. ; Debelouchina, Galia T. ; Kayatekin, Can ; Dorminy, Tea ; Jacavone, Angela C. ; Griffin, Robert G. ; Lindquist, Susan. / Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics. In: Chemistry and Biology. 2014 ; Vol. 21, No. 2. pp. 295-305.
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