Early-Stage Oligomerization of Prion-like Polypeptides Reveals the Molecular Mechanism of Amyloid-Disrupting Capacity by Proline Residues.

ABSTRACT: Proline cis/trans isomerization governs protein local conformational changes via its local mechanical rigidity. The amyloid-disrupting capacity of proline is widely acknowledged; however, the molecular mechanism is still not clear. To understand how proline residues in polypeptide chains influence amyloid propensity, we study several truncated sequences of the TDP-43 C-terminal region (287-322) and their triple proline variants (³⁰⁸PPP³¹⁰). We use coarse-grained molecular simulation to study the time evolution of the process of aggregation in the early stages in an effective high-concentration condition (∼25 mM). This ensures the long time scales for protein association at laboratory concentrations. We use several experimentally determined structure temp

SUBMITTER: Lin TY 

PROVIDER: S-EPMC9924260 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature