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Impact of the tail and mutations G131V and M129V on prion protein flexibility
Author(s) -
Santini Sébastien,
Claude JeanBaptiste,
Audic Stéphane,
Derreumaux Philippe
Publication year - 2003
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10348
Subject(s) - point mutation , beta sheet , molecular dynamics , biophysics , flexibility (engineering) , mutation , protein structure , prion protein , chemistry , biology , biochemistry , gene , computational chemistry , medicine , statistics , disease , pathology , mathematics
Abstract Within the “protein‐only” hypothesis, a detailed mechanism for the conversion of a α‐helix to β‐sheet structure is unclear. We have investigated the effects of the tail 90–123 and the point mutations G131V and M129V on prion protein conformational plasticity at neutral pH. Molecular dynamics simulations show that the dynamics of the core 124–226 is essentially independent of the tail and that the point mutation G131V does not affect PrP thermodynamic stability. Both mutations, however, enhance the flexibility of residues that participate in the two‐step process for prion propagation. They also extend the short β‐sheet in the normal protein into a larger sheet at neutral pH. This finding suggests a critical role of the tail for triggering the topological change. Proteins 2003;51:258–265. © 2003 Wiley‐Liss, Inc.