Comparative molecular dynamics simulations of pathogenic and non-pathogenic huntingtin protein monomers and dimers.

ABSTRACT: Polyglutamine expansion at the N-terminus of the huntingtin protein exon 1 (Htt-ex1) is closely associated with a number of neurodegenerative diseases, which result from the aggregation of the increased polyQ repeat. However, the underlying structures and aggregation mechanism are still poorly understood. We performed microsecond-long all-atom molecular dynamics simulations to study the folding and dimerization of Htt-ex1 (about 100 residues) with non-pathogenic and pathogenic polyQ lengths, and uncovered substantial differences. The non-pathogenic monomer adopts a long α-helix that includes most of the polyQ residues, which forms the interaction interface for dimerization, and a PPII-turn-PPII motif in the proline-rich region. In the pathogenic monomer, the polyQ region is disorder

SUBMITTER: Khaled M 

PROVIDER: S-EPMC10123271 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature