Classical dynamins harbor two additional domains that dynamin-related proteins typically lack: a highly conserved pleckstrin-homology (PH) domain that confers binding to negatively charged lipids via its flexible regions (Ferguson et al., 1994)(supplementary material Fig. S2A, B) and a proline-rich domain (PRD) that is the binding site for proteins that interact with dynamins via Src-homology 3 (SH3) domains. Several of the dynamin-related proteins vary in their domain structure to accommodate for specific functional requirements; for example, some dynaminrelated proteins contain membrane-spanning regions or organelle-targeting sequences (panels 3a-c in the poster).

Compared with Ras-GTPases, the GTPase domain of classical dynamins has a lower affinity for nucleotides and displays higher hydrolysis rates. In addition, the GTPase domain of dynamins exhibits cooperativity of GTP hydrolysis upon dynamin oligomerization. Thus, in vitro rates of hydrolysis increase by one to two orders of magnitude when dynamin self-assembles into helical arrays around lipid tubes (Song et al., 2004). Interactions between the GTPase domain, the middle domain and the GED drive this self-assembly process, whereas the PH domain provides affinity for lipid (panel 1b in the poster). Upon hydrolysis of GTP, dynamin undergoes a conformational change that leads to a decrease in the helix diameter, thereby constricting and twisting the enclosed lipid tube (Danino et al., 2004; Roux et al., 2006)(panel 5 in the poster). These observations suggest that dynamin translates the scalar chemical process of GTP hydrolysis into a vectorial physical force–that is, it exhibits mechano-enzymatic properties (Hinshaw, 2000). In vitro, multiple rounds of GTP hydrolysis lead to the disassembly of dynamin oligomers and their release from the lipid bilayer (Danino et al., 2004). The results of recent light-microscopy studies suggest that dynamin alone could be sufficient for membrane fission in vitro (Bashkirov et al., 2008; Pucadyil and Schmid, 2008).