Prion protein: evolution caught en route.

TitlePrion protein: evolution caught en route.
Publication TypeJournal Article
Year of Publication2001
AuthorsTompa, P., G. E. Tusnády, M. Cserzo, and I. Simon
JournalProc Natl Acad Sci U S A
Date Published2001 Apr 10
KeywordsEvolution, Molecular, Prions, Protein Conformation

The prion protein displays a unique structural ambiguity in that it can adopt multiple stable conformations under physiological conditions. In our view, this puzzling feature resulted from a sudden environmental change in evolution when the prion, previously an integral membrane protein, got expelled into the extracellular space. Analysis of known vertebrate prions unveils a primordial transmembrane protein encrypted in their sequence, underlying this relocalization hypothesis. Apparently, the time elapsed since this event was insufficient to create a "minimally frustrated" sequence in the new milieu, probably due to the functional constraints set by the importance of the very flexibility that was created in the relocalization. This scenario may explain why, in a structural sense, the prion protein is still en route toward becoming a foldable globular protein.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID11287647
PubMed Central IDPMC31852