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Prion protein: evolution caught en route.

ABSTRACT: 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.

SUBMITTER: Tompa P

PROVIDER: S-EPMC31852 | biostudies-literature | 2001 Apr

REPOSITORIES: biostudies-literature

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Prion protein: evolution caught en route.

Tompa P P Tusnády G E GE Cserzo M M Simon I I

Proceedings of the National Academy of Sciences of the United States of America 20010403 8

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 t ...[more]

PMID: 11287647

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