A model for dynamin self-assembly based on binding between three differentprotein domains

Dynamin is a 100-kDa GTPase that assembles into multimeric spirals at the n ecks of budding clathrin-coated vesicles. We describe three different intra molecular binding interactions that may account for the process of dynamin self-assembly. The first binding interaction is the dimerization of a 100-a mino acid segment in the C-terminal half of dynamin. We call this segment t he assembly domain, because it appears to be critical for multimerization. The second binding interaction occurs between the assembly domain and the N -terminal GTPase domain The strength of this interaction is controlled by t he nucleotide-bound state of the GTPase domain, as shown with mutations in GTP binding motifs and in vitro binding experiments. The third binding inte raction occurs between the assembly domain and a segment that we call the m iddle domain. This is the segment between the N-terminal GTPase domain and the pleckstrin homology domain The three different binding interactions sug gest a model in which dynamin molecules first dimerize. The dimers are then linked into a chain by a second binding reaction. The third binding intera ction might connect adjacent rungs of the spiral.