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

ABSTRACT: We have studied both the Spy and the FKBP protein-ligand systems by structural proteomics and molecular -dynamics simulations. We have used hydrogen/deuterium exchange, differential crosslinking, and surface modification to characterize the conformational changes that occur upon both peptide binding (Im7 with Spy) and small molecule binding (rapamycin with FKBP) to the protein. We have shown that, in both cases, the proteins are considerably disordered but their structures are different from the unfolded structure obtained with 8M urea in solution, and both proteins undergo a dramatic increase in secondary structure content upon ligand binding.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Escherichia Coli

SUBMITTER: Karl Makepeace

LAB HEAD: Christoph H. Borchers

PROVIDER: PXD015275 | Pride | 2021-09-08

REPOSITORIES: Pride

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

Makepeace Karl A T KAT Brodie Nicholas I NI Popov Konstantin I KI Gudavicius Geoff G Nelson Christopher J CJ Petrotchenko Evgeniy V EV Dokholyan Nikolay V NV Borchers Christoph H CH

Journal of proteomics 20191101

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 ...[more]

PMID: 31683063

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