Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2
Authors
- C. Shah
- B.G. Hegde
- B. Morén
- E. Behrmann
- T. Mielke
- G. Moenke
- C.M. Spahn
- R. Lundmark
- O. Daumke
- R. Langen
Journal
- Structure
Citation
- Structure 22 (3): 409-420
Abstract
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.