Ligand-induced disorder-to-order transitions characterized by structural proteomics and molecular dynamics simulations.

ABSTRACT: For disordered proteins, ligand binding can be a critical event that changes their structural dynamics. The ability to characterize such changes would facilitate the development of drugs designed to stabilize disordered proteins, whose mis-folding is important for a number of pathologies, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. In this study, we used hydrogen/deuterium exchange, differential crosslinking, differential surface modification, and molecular dynamics (MD) simulations to characterize the structural changes in disordered proteins that result from ligand binding. We show here that both an ATP-independent protein chaperone, Spy L32P, and the FK506 binding domain of a prolyl isomerase, FKBP-25 F145A/I223P, are disordered, yet exhibit struct

SUBMITTER: Makepeace KAT 

PROVIDER: S-EPMC6878985 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature