Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics.
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.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kendra K
KK
Frederick
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Francis Bitter Magnet Labaratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Galia T
GT
Debelouchina
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Can
C
Kayatekin
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Tea
T
Dorminy
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Francis Bitter Magnet Labaratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Angela C
AC
Jacavone
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Francis Bitter Magnet Labaratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Robert G
RG
Griffin
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: lindquist_admin@wi.mit.edu.
Susan
S
Lindquist
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010454:Peptide Termination Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000682:Amyloid; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins