Identification and function of conformational dynamics in the multidomain GTPase dynamin.

ABSTRACT: Vesicle release upon endocytosis requires membrane fission, catalyzed by the large GTPase dynamin. Dynamin contains five domains that together orchestrate its mechanochemical activity. Hydrogen-deuterium exchange coupled with mass spectrometry revealed global nucleotide- and membrane-binding-dependent conformational changes, as well as the existence of an allosteric relay element in the α2(S) helix of the dynamin stalk domain. As predicted from structural studies, FRET analyses detect large movements of the pleckstrin homology domain (PHD) from a 'closed' conformation docked near the stalk to an 'open' conformation able to interact with membranes. We engineered dynamin constructs locked in either the closed or open state by chemical cross-linking or deletion mutagenesis and showed that PHD

SUBMITTER: Srinivasan S 

PROVIDER: S-EPMC4755114 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature