Structure and Dynamics of the Misfolding Intermediate in the Pathogenic T183A Prion Protein Mutant.

ABSTRACT: Characterizing high-energy conformations in protein molecules is crucial to delineate the nature of dynamic processes that underlie biological activity, as these elusive species often play critical roles in fundamental mechanisms of the cell, such as enzyme catalysis or protein folding and aggregation, among many others. In this context, the integration of molecular simulations with experimental biophysics represents a powerful strategy to delineate complex conformational landscapes, enabling the study of transient conformations at atomic resolution. Here, we characterized intermediate states along the misfolding pathway of the human prion protein (PrP) variant T183A, which is associated with familial Creutzfeldt-Jakob disease. Using replica-averaged molecular dynamics simulations, restrai

SUBMITTER: Biancaniello C 

PROVIDER: S-EPMC12529898 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature