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

Journal Article · Mon Jun 14 04:00:00 EDT 2010 · Nature

DOI:https://doi.org/10.1038/nature09032· OSTI ID:1002453

Chappie, Joshua S; Acharya, Sharmistha; Leonard, Marilyn; Schmid, Sandra L; Dyda, Fred ^[1]

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1. NIH

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 {angstrom} 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.AlF{sub 4}{sup -}. 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002453
• Journal Information: Nature, Journal Name: Nature Journal Issue: 2010 Vol. 465
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ARGININE
CATIONS
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
DIMERIZATION
DIMERS
FISSION
HYDROLYSIS
MACHINERY
MEMBRANES
PROTEINS
RESOLUTION
SODIUM IONS