Atomic insights into the effects of pathological mutants through the disruption of hydrophobic core in the prion protein.

ABSTRACT: Destabilization of prion protein induces a conformational change from normal prion protein (PrP^C) to abnormal prion protein (PrP^SC). Hydrophobic interaction is the main driving force for protein folding, and critically affects the stability and solvability. To examine the importance of the hydrophobic core in the PrP, we chose six amino acids (V176, V180, T183, V210, I215, and Y218) that make up the hydrophobic core at the middle of the H2-H3 bundle. A few pathological mutants of these amino acids have been reported, such as V176G, V180I, T183A, V210I, I215V, and Y218N. We focused on how these pathologic mutations affect the hydrophobic core and thermostability of PrP. For this, we ran a temperature-based replica-exchange molecular dynamics (T-REMD) simulation, with a

SUBMITTER: Lee J 

PROVIDER: S-EPMC6915724 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature