Structural Insights into Membrane Interaction and Caveolar Targeting of Dynamin-like EHD2

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• 作者：Claudio Shah¹ ; ² ; ⁸ ; Balachandra G. Hegde³ ; ⁸ ; Bjö ; rn Moré ; n⁴ ; Elmar Behrmann⁵ ; Thorsten Mielke⁵ ; ⁶ ; Gregor Moenke¹ ; Christian M.T. Spahn⁵ ; Richard Lundmark⁴ ; Oliver Daumke¹ ; ² ; ⁵ ; ^{oliver.daumke@mdc-berlin.de" class="auth_mail} ; Ralf Langen⁷ ; ^{langen@med.usc.edu" class="auth_mail}
• 刊名：Structure
• 出版年：4 March, 2014
• 年：2014
• 卷：22
• 期：3
• 页码：409-420
• 全文大小：3271 K

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Summary

The dynamin-related Eps15-homology domain-containing聽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.