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

Article

关键词: DEPENDENT CONFORMATIONAL-CHANGES;    ISOMORPHOUS REPLACEMENT;    CRYSTAL-STRUCTURE;    PROTEINS;    BINDING;    CONSTRICTION;    MECHANISM;    MODEL;    SUPERFAMILY;    HYDROLYSIS;   

DOI  :  10.1038/nature09032

来源: SCIE

【 摘 要 】

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.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.

【 授权许可】

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