Structural insight into conformational change in prion protein by breakage of electrostatic network around H187 due to its protonation.

ABSTRACT: A conformational change from normal prion protein(PrP^C) to abnormal prion protein(PrP^SC) induces fatal neurodegenerative diseases. Acidic pH is well-known factors involved in the conformational change. Because the protonation of H187 is strongly linked to the change in PrP stability, we examined the charged residues R156, E196, and D202 around H187. Interestingly, there have been reports on pathological mutants, such as H187R, E196A, and D202N. In this study, we focused on how an acidic pH and pathological mutants disrupt this electrostatic network and how this broken network destabilizes PrP structure. To do so, we performed a temperature-based replica-exchange molecular dynamics (T-REMD) simulation using a cumulative 252 μs simulation time. We measured the distance

SUBMITTER: Lee J 

PROVIDER: S-EPMC6917724 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature