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


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.

SUBMITTER: Shah C 

PROVIDER: S-EPMC3979964 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Shah Claudio C   Hegde Balachandra G BG   Morén Björn B   Behrmann Elmar E   Mielke Thorsten T   Moenke Gregor G   Spahn Christian M T CMT   Lundmark Richard R   Daumke Oliver O   Langen Ralf R  

Structure (London, England : 1993) 20140206 3


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 h  ...[more]

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