Dynamin is a large, extended protein consisting of five domains. We have recently determined the 2.0 Angstrom resolution crystal structure of a human dynamin 1-derived minimal GTPase-GED (for """"""""GTPase effector domain"""""""") fusion protein. This fusion protein dimerizes in the presence of the transition state mimic GDP-aluminum fluoride. The structure reveals dynamin's catalytic machinery and explains how assembly-stimulated GTP hydrolysis is achieved through G domain dimerization. Particularly intriguing was the identification of a sodium ion in the active site, suggesting that dynamin uses a cation to compensate for the developing negative in the transition state and providing a rationale for the inability to previously implicate a more-usual arginine finger. The structure of this fusion domain allows us to provide a model for the role of dimerization during dynamin-catalyzed membrane fission.
|Chappie, Joshua S; Dyda, Fred (2013) Building a fission machine - structural insights into dynamin assembly and activation. J Cell Sci 126:2773-84|
|Chappie, Joshua S; Mears, Jason A; Fang, Shunming et al. (2011) A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke. Cell 147:209-22|
|Chappie, Joshua S; Acharya, Sharmistha; Leonard, Marilyn et al. (2010) G domain dimerization controls dynamin's assembly-stimulated GTPase activity. Nature 465:435-40|