Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2
2014 (English)In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 22, no 3, 409-420 p.Article in journal (Refereed) Published
The dynamin-related Eps15-homology domain-containing protein 2 (EHD2) is a membrane-remodeling ATPase that regulates the dynamics of caveolae. Here, we established an electron paramagnetic resonance (EPR) approach to characterize structural features of membrane-bound EHD2. We show that residues at the tip of the helical domain can insert into the membrane and may create membrane curvature by a wedging mechanism. Using EPR and X-ray crystallography, we found that the N terminus is folded into a hydrophobic pocket of the GTPase domain in solution and can be released into the membrane. Cryoelectron microscopy demonstrated that the N terminus is not essential for oligomerization of EHD2 into a membrane-anchored scaffold. Instead, we found a function of the N terminus in regulating targeting and stable association of EHD2 to caveolae. Our data uncover an unexpected, membrane-induced regulatory switch in EHD2 and demonstrate the versatility of EPR to study structure and function of dynamin superfamily proteins.
Place, publisher, year, edition, pages
2014. Vol. 22, no 3, 409-420 p.
Cell Biology Biophysics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:umu:diva-88288DOI: 10.1016/j.str.2013.12.015ISI: 000333025700007PubMedID: 24508342OAI: oai:DiVA.org:umu-88288DiVA: diva2:715470