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

Dynamin is an atypical GTPase that catalyses membrane fission during clathrin-mediated endocytosis. The mechanisms of dynamin’s 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 dynamin’s 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.

• Publication year

  2010

• Venue

  Nature

• Publication date

  2010-04-28

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/nature09032PMID 20428113PMCID 2879890
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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