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

Nature. 2010 May 27;465(7297):435-40. doi: 10.1038/nature09032. Epub 2010 Apr 28.


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 A 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(4)(-).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 types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aluminum Compounds / metabolism
  • Amino Acid Sequence
  • Biocatalysis
  • Catalytic Domain / genetics
  • Conserved Sequence
  • Crystallography, X-Ray
  • Dynamin I / chemistry*
  • Dynamin I / genetics
  • Dynamin I / metabolism*
  • Enzyme Activation
  • Fluorides / metabolism
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / metabolism
  • Humans
  • Hydrolysis
  • Models, Molecular
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sodium / metabolism


  • Aluminum Compounds
  • Guanosine Diphosphate
  • tetrafluoroaluminate
  • Sodium
  • Dynamin I
  • GTP Phosphohydrolases
  • Fluorides

Associated data

  • PDB/1JWY
  • PDB/2AKA
  • PDB/2B92
  • PDB/2GJ8
  • PDB/2X2E
  • PDB/2X2F