Conversion of Helix 1 into a Loop in Prion Protein Misfolding.

ABSTRACT: Cellular prion protein PrP^C consists of three α-helices, one β-sheet, and an unstructured N-terminal domain. Misfolding of this protein into the scrapie form (PrP^Sc) increases dramatically the β-sheet content. H1 is the most stable helix on PrP^C and contains an unusual number of hydrophilic amino acids. Its fate in PrP^Sc is not clear. We performed replica exchange molecular dynamics simulations on H1 alone, H1 together with an N-terminally flanking H1B1 loop and H1 in complex with other hydrophilic regions of the prion protein. In the presence of the H⁹⁹SQWNKPSKPKTNMK¹¹³ sequence, H1 is almost completely converted to a loop structure stabilized by a network of salt bridges. On the other hand, H1 retains its helical structure

SUBMITTER: Tavsanlı A 

PROVIDER: S-EPMC9948551 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature