Assembly_GED domains of Dynamin

Middle + GED

Dynamin assembly

Above is the domain structure of a dynamin dimer where the small arrows indicate intra-molecular interactions between domains.

The overall shape of dynamin on liposomes looks like a T-Bar, by electron microscopy

The middle and GED domains are known as 'Assembly domains' because they are important for dynamin dimerisation and further oligomerisation. They can both interact with the GTPase domains and the GED can interact with itself. Some of these interactions will be intra- and some may be inter-molecular and thus some will be important for dimerisation and some may be important for further oligomerisation. As illustrated above, in many of our experiments dynamin is a stable dimer, and thus the building bock of the oligomeric structure that forms on liposomes or tubules (see below). By electron microscopy a dynamin dimer is seen as a T-bar-like structure (see above) where the the PH domain is at the base of the T and is closest to the membrane.

Cartoon of how dynamin assembles according to electron microscopy

In low ionic strength dynamin assembles into rings and stacks of rings, while on liposome dynamin constricts the liposomes into tubules and forms a continuous helical array. In these assembled forms of dynamin the assembly stimulates GTP hydrolysis and it is likely that there are further interactions with the GTPase domain or a conformational change that is sensed by the GTPase domain.

Mutations in the GED of dynamin that affect oligomerisation (and not dimerisation) in vitro and in vivo (see Marks et al 2001) show that this domain is important for assembly.

Oligomerisation has implications for the overexpression of dynamin in cells. The effect of mutant dynamin overexpression is often referred to as being ‘dominant’. This could be due to the depletion of binding partners but is more likely an indirect effect due to co-oligomerisation with endogenous wild-type protein. Thus when overexpressing dynamin mutants on a wild-type background we assume that the mutants form mixed dimers and tetramers with the endogenous wild-type dynamin. These mutants may thus disrupt oligomerisation and/or the cooperativity of oligomerisation-stimulated GTP hydrolysis.

We would still like to understand how does oligomerisation stimulated GTPase activation occurs (see tubulin) and see also discussion of 'arginine finger' under GTP binding residues.

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