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, vesi cle trafficking and maintenance of mitochondrial morphology. In contrast to the classical switch GTPases, a force-generating function has been suggest ed for dynamins. Here we report the 2.3 Angstrom crystal structure of the n ucleotide-free and GDP-bound GTPase domain of Dictyostelium discoideum dyna min A. The GTPase domain is the most highly conserved region among dynamins . The globular structure contains the G-protein core fold, which is extende d from a six-stranded beta -sheet to an eight-stranded one by a 55 amino ac id insertion. This topologically unique insertion distinguishes dynamins fr om other subfamilies of GTP-binding proteins. An additional N-terminal heli x interacts with the C-terminal helix of the GTPase domain, forming a hydro phobic groove, which could be occupied by C-terminal parts of dynamin not p resent in our construct. The lack of major conformational changes between t he nucleotide-free and the GDP-bound state suggests that mechanochemical re arrangements in dynamin occur during GTP binding, GTP hydrolysis or phospha te release and are not linked to loss of GDP.