E. Smirnova et al., A model for dynamin self-assembly based on binding between three differentprotein domains, J BIOL CHEM, 274(21), 1999, pp. 14942-14947
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.