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Exploring structural and thermodynamic stabilities of human prion protein pathogenic mutants D202N, E211Q and Q217R.
Guo, Jingjing; Ren, Hui; Ning, Lulu; Liu, Huanxiang; Yao, Xiaojun.
Afiliação
  • Guo J; State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, China.
J Struct Biol ; 178(3): 225-32, 2012 Jun.
Article em En | MEDLINE | ID: mdl-22491059
ABSTRACT
The central event in the pathogenesis of prion protein (PrP) is a profound conformational change from its α-helical (PrP(C)) to its ß-sheet-rich isoform (PrP(Sc)). Many single amino acid mutations of PrP are associated with familial prion diseases, such as D202N, E211Q, and Q217R mutations located at the third native α-helix of human PrP. In order to explore the underlying structural and dynamic effects of these mutations, we performed all-atom molecular dynamics (MD) simulations for the wild-type (WT) PrP and its mutants. The obtained results indicate that these amino acid substitutions have subtle effects on the protein structures, but show large changes of the overall electrostatic potential distributions. We can infer that the changes of PrP electrostatic surface due to the studied mutations may influence the intermolecular interactions during the aggregation process. In addition, the mutations also affect the thermodynamic stabilities of PrP.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Príons / Simulação de Dinâmica Molecular Limite: Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Príons / Simulação de Dinâmica Molecular Limite: Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article