TY - JOUR
T1 - Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics
AU - Frederick, Kendra K.
AU - Debelouchina, Galia T.
AU - Kayatekin, Can
AU - Dorminy, Tea
AU - Jacavone, Angela C.
AU - Griffin, Robert G.
AU - Lindquist, Susan
N1 - Funding Information:
We thank members of the Lindquist and Griffin laboratories for comments on the manuscript. We thank Dr. Marvin Bayro for helpful discussions and Dr. Yossi Farjoun for input on algorithm design. S.L. is an investigator of the Howard Hughes Medical Institute. K.K.F. is an HHMI fellow of the Life Science Research Foundation. This work was supported by US National Institutes of Health grants GM025874 to S.L. and EB003151 and EB002026 to R.G.G.
PY - 2014/2/20
Y1 - 2014/2/20
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2013.12.013
DO - 10.1016/j.chembiol.2013.12.013
M3 - Article
C2 - 24485763
AN - SCOPUS:84894486685
SN - 1074-5521
VL - 21
SP - 295
EP - 305
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 2
ER -