G domain dimerization controls dynamin's assembly-stimulated GTPase activity

Joshua S. Chappie, Sharmistha Acharya, Marilyn Leonard, Sandra L. Schmid, Fred Dyda

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

Dynamin is an atypical GTPase that catalyses membrane fission during clathrin-mediated endocytosis. The mechanisms of dynamins basal and assembly-stimulated GTP hydrolysis are unknown, though both are indirectly influenced by the GTPase effector domain (GED). Here we present the 2.0 Å resolution crystal structure of a human dynamin 1-derived minimal GTPase-GED fusion protein, which was dimeric in the presence of the transition state mimic GDP.AlF4-.The structure reveals dynamins catalytic machinery and explains how assembly-stimulated GTP hydrolysis is achieved through G domain dimerization. A sodium ion present in the active site suggests that dynamin uses a cation to compensate for the developing negative charge in the transition state in the absence of an arginine finger. Structural comparison to the rat dynamin G domain reveals key conformational changes that promote G domain dimerization and stimulated hydrolysis. The structure of the GTPase-GED fusion protein dimer provides insight into the mechanisms underlying dynamin-catalysed membrane fission.

Original languageEnglish (US)
Pages (from-to)435-440
Number of pages6
JournalNature
Volume465
Issue number7297
DOIs
StatePublished - May 27 2010

ASJC Scopus subject areas

  • General

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