Comparative computational analysis of prion proteins reveals two fragments with unusual structural properties and a pattern of increase in hydrophobicity associated with disease-promoting mutations.

ABSTRACT: Prion diseases are a group of neurodegenerative disorders associated with conversion of a normal prion protein, PrPC, into a pathogenic conformation, PrPSc. The PrPSc is thought to promote the conversion of PrPC. The structure and stability of PrPC are well characterized, whereas little is known about the structure of PrPSc, what parts of PrPC undergo conformational transition, or how mutations facilitate this transition. We use a computational knowledge-based approach to analyze the intrinsic structural propensities of the C-terminal domain of PrP and gain insights into possible mechanisms of structural conversion. We compare the properties of PrP sequences to those of a PrP paralog, Doppel, and to the distributions of structural propensities observed in known protein structures from the

SUBMITTER: Kuznetsov IB 

PROVIDER: S-EPMC2287303 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature