Nucleated conformational conversion and the replication of conformational information by a prion determinant.
Prion proteins can serve as genetic elements by adopting distinct physical and functional states that are self-perpetuating and heritable. The critical region of one prion protein, Sup35, is initially unstructured in solution and then forms self-seeded amyloid fibers. We examined in vitro the mechanism by which this state is attained and replicated. Structurally fluid oligomeric complexes appear to be crucial intermediates in de novo amyloid nucleus formation. Rapid assembly ensues when these complexes conformationally convert upon association with nuclei. This model for replicating protein-based genetic information, nucleated conformational conversion, may be applicable to other protein assembly processes.
Serio
T R
TR
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
Cashikar
A G
AG
Kowal
A S
AS
Sawicki
G J
GJ
Moslehi
J J
JJ
Serpell
L
L
Arnsdorf
M F
MF
Lindquist
S L
SL
D000682:Amyloid / Q000737:chemistry*; D001704:Biopolymers / Q000737:chemistry; D002499:Centrifugation, Density Gradient; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008027:Light; D008823:Micelles; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D008956:Models, Chemical; D010454:Peptide Termination Factors; D011328:Prions / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011487:Protein Conformation; D017510:Protein Folding; D029701:Saccharomyces cerevisiae Proteins; D012542:Scattering, Radiation; D012995:Solubility; D013010:Sonication
D000682:Amyloid; D001704:Biopolymers; D005656:Fungal Proteins; D008823:Micelles; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D010450:Endopeptidases