Transient exposure of a buried phosphorylation site in an autoinhibited protein.

ABSTRACT: Autoinhibition is a mechanism used to regulate protein function, often by making functional sites inaccessible through the interaction with a cis-acting inhibitory domain. Such autoinhibitory domains often display a substantial degree of structural disorder when unbound, and only become structured in the inhibited state. These conformational dynamics make it difficult to study the structural origin of regulation, including effects of regulatory post-translational modifications. Here, we study the autoinhibition of the Dbl Homology domain in the protein Vav1 by the so-called acidic inhibitory domain. We use molecular simulations to study the process by which a mostly unstructured inhibitory domain folds upon binding and how transient exposure of a key buried tyrosine residue makes it access

SUBMITTER: Orioli S 

PROVIDER: S-EPMC8758417 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature