Effects of the pathogenic mutation A117V and the protective mutation H111S on the folding and aggregation of PrP106-126: Insights from replica exchange molecular dynamics simulations

Lulu Ning, Dabo Pan, Yan Zhang, Shaopeng Wang, Huanxiang Liu, Xiaojun Yao

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The fragment 106-126 of prion protein exhibits similar properties to full-length prion. Experiments have shown that the A117V mutation enhances the aggregation of PrP106-126, while the H111S mutation abolishes the assembly. However, the mechanism of the change in the aggregation behavior of PrP106-126 upon the two mutations is not fully understood. In this study, replica exchange molecular dynamics simulations were performed to investigate the conformational ensemble of the WT PrP106-126 and its two mutants A117V and H111S. The obtained results indicate that the three species are all intrinsically disordered but they have distinct morphological differences. The A117V mutant has a higher propensity to form β-hairpin structures than the WT, while the H111S mutant has a higher population of helical structures. Furthermore, the A117V mutation increases the hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation reduces the exposure of hydrophobic residues. It can be concluded that the difference in populations of β-hairpin structures and the change of hydrophobic solvent accessible areas may induce the different aggregation behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the two mutations have contrary effects on the aggregation of PrP106-126 is very meaningful for further elucidation of the mechanism underlying aggregation and design of inhibitor against aggregation process.

Original languageEnglish
Article numbere0125899
JournalPLoS ONE
Volume10
Issue number5
DOIs
Publication statusPublished - 20 May 2015
Externally publishedYes

Fingerprint

Dive into the research topics of 'Effects of the pathogenic mutation A117V and the protective mutation H111S on the folding and aggregation of PrP106-126: Insights from replica exchange molecular dynamics simulations'. Together they form a unique fingerprint.

Cite this