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 critica l region of one prion protein, Sup35, is initially unstructured in solution and then forms self-seeded amyloid fibers. We examined in vitro the mechan ism by which this state is attained and replicated. Structurally fluid olig omeric complexes appear to be crucial intermediates in de novo amyloid nucl eus formation. Rapid assembly ensues when these complexes conformationally convert. upon association with nuclei. This model for replicating protein-b ased genetic information. nucleated conformational conversion, may be appli cable to other protein assembly processes.