Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2.

Claudio Shah, Balachandra G Hegde, Björn Morén, Elmar Behrmann, Thorsten Mielke, Gregor Moenke, Christian M T Spahn, Richard Lundmark, Oliver Daumke, Ralf Langen

Structure (London, England : 1993) 2014 Mar 04

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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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Citation

Claudio Shah, Balachandra G Hegde, Björn Morén, Elmar Behrmann, Thorsten Mielke, Gregor Moenke, Christian M T Spahn, Richard Lundmark, Oliver Daumke, Ralf Langen. Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2. Structure (London, England : 1993). 2014 Mar 04;22(3):409-420