Crystal structure of a dynamin GTPase domain in both nucleotide-free and GDP-bound forms.
Dynamins form a family of multidomain GTPases involved in endocytosis, vesicle trafficking and maintenance of mitochondrial morphology. In contrast to the classical switch GTPases, a force-generating function has been suggested for dynamins. Here we report the 2.3 A crystal structure of the nucleotide-free and GDP-bound GTPase domain of Dictyostelium discoideum dynamin A. The GTPase domain is the most highly conserved region among dynamins. The globular structure contains the G-protein core fold, which is extended from a six-stranded beta-sheet to an eight-stranded one by a 55 amino acid insertion. This topologically unique insertion distinguishes dynamins from other subfamilies of GTP-binding proteins. An additional N-terminal helix interacts with the C-terminal helix of the GTPase domain, forming a hydrophobic groove, which could be occupied by C-terminal parts of dynamin not present in our construct. The lack of major conformational changes between the nucleotide-free and the GDP-bound state suggests that mechanochemical rearrangements in dynamin occur during GTP binding, GTP hydrolysis or phosphate release and are not linked to loss of GDP.
Niemann
H H
HH
Department of Biophysics, Max-Planck-Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany.
Knetsch
M L
ML
Scherer
A
A
Manstein
D J
DJ
Kull
F J
FJ
D001665:Binding Sites / Q000502:physiology; D018360:Crystallography, X-Ray; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000502:physiology; D015800:Protozoan Proteins; D017386:Sequence Homology, Amino Acid
D009711:Nucleotides; D015800:Protozoan Proteins; D006153:Guanosine Diphosphate; D020558:GTP Phosphohydrolases; D034281:Dynamins; C117420:dynamin A protein, Dictyostelium discoideum