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 journalArticle

172 Citations (Scopus)

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

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Dynamins
GTP Phosphohydrolases
Dimerization
Hydrolysis
Guanosine Triphosphate
Dynamin I
Clathrin
Membranes
Endocytosis
Fingers
Arginine
Cations
Catalytic Domain
Sodium
Ions

ASJC Scopus subject areas

  • General

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G domain dimerization controls dynamin's assembly-stimulated GTPase activity. / Chappie, Joshua S.; Acharya, Sharmistha; Leonard, Marilyn; Schmid, Sandra L.; Dyda, Fred.

In: Nature, Vol. 465, No. 7297, 27.05.2010, p. 435-440.

Research output: Contribution to journalArticle

Chappie, JS, Acharya, S, Leonard, M, Schmid, SL & Dyda, F 2010, 'G domain dimerization controls dynamin's assembly-stimulated GTPase activity', Nature, vol. 465, no. 7297, pp. 435-440. https://doi.org/10.1038/nature09032
Chappie, Joshua S. ; Acharya, Sharmistha ; Leonard, Marilyn ; Schmid, Sandra L. ; Dyda, Fred. / G domain dimerization controls dynamin's assembly-stimulated GTPase activity. In: Nature. 2010 ; Vol. 465, No. 7297. pp. 435-440.
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