Conformational distortions induced by periodically recurring A…A in d(CAG).d(CAG) provide stereochemical rationale for the trapping of MSH2.MSH3 in polyQ disorders.

ABSTRACT: CAG repeat instability causes a number of neurodegenerative disorders. The unusual hairpin stem structure formed by the CAG repeats in DNA traps the human mismatch repair MSH2.MSH3 (Mutsβ) complex. To understand the mechanism behind the abnormal binding of Mutsβ with the imperfect hairpin stem structure formed by CAG repeats, molecular dynamics simulations have been carried out for Mutsβ-d(CAG)₂(CAG)(CAG)₂.d(CTG)₂(CAG)(CTG)₂ (1 A…A mismatch) and Mutsβ-d(CAG)₅.d(CAG)₅ (5 mismatches, wherein, A…A occurs periodically) complexes. The interaction of MSH3 residue Tyr₂₄₅ at the minor groove side of A…A, an essential interaction responsible for the recognition by Mutsβ, are retained in both the cases. Nevertheless, the pe

SUBMITTER: Ajjugal Y 

PROVIDER: S-EPMC8379282 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature