Members of the EHD family are ubiquitously expressed dynamin-related ATPases which are built of an amino-terminal GTPase domain, followed by a helical domain and a carboxy-terminal regulatory Eps15 homology (EH) domain. EHDs can be found at vesicular and tubular membrane structures in the cell, and they are implicated in the control of several trafficking pathways including the exit of cargo proteins from the endocytic recycling compartment.
We showed that also EHD2 oligomerizes in ring-like structures around tubulated liposomes. By solving the crystal structure of an EHD2 dimer, we found that stable dimerization of EHD2 is mediated via a highly conserved interface in the GTPase domain. The lipid-binding sites in each dimer are located at the tip of the helical domains and create a highly curved lipid interaction site. Based on a biochemical analysis, we suggested a structural model for EHD2 oligomeric rings. These rings have a remarkably different architecture compared to the rings formed by MxA, dynamin and DNM1L. Furthermore, we found EHD2 as a novel integral component of caveolae which are flask-shaped invaginations of the plasma membrane involved in buffering membrane tension. This work opens up a wide range of cell-based approaches to study the physiological function of this protein.
Daumke O., Lundmark R., Vallis Y., Martens S., Butler P.J., McMahon H.M. (2007) Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling. Nature 449, 923-927
Morén B., Shah C., Howes M.T., Schieber N.L., McMahon H.T., Parton R.G., Daumke O., Lundmark R. (2012) EHD2 regulates caveola dynamics via ATP-driven targeting and oligomerization. Mol Biol Cell 23, 1316-29
Reseacher in my group
Claudio Shah (PhD 2013)
Richard Lundmark (University of Umeå, Ralf Langen (University of Los Angeles), Harvey McMahon (Laboratory of Molecular Biology, Cambridge).
Figure 1: a) EHD2 oligomerization around negatively-charged liposomes inducing tubulation. Note the ring-like oligomers formed by EHD2. b) Crystal structure of the EHD2 dimer assembled via an alternative site in the GTPase domain. c) Proposed oligomerization model of EHD2.