4cid | pdb_00004cid
Structural insights into the N-terminus of the EHD2 ATPase
Structural highlights
FunctionEHD2_MOUSE Plays a role in membrane reorganization in response to nucleotide hydrolysis. Binds to liposomes and deforms them into tubules. Plays a role in membrane trafficking between the plasma membrane and endosomes. Important for the internalization of GLUT4. Required for normal fusion of myoblasts to skeletal muscle myotubes. Binds ATP; does not bind GTP.[1] [2] Publication Abstract from PubMedThe 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. Structural Insights into Membrane Interaction and Caveolar Targeting of Dynamin-like EHD2.,Shah C, Hegde BG, Moren B, Behrmann E, Mielke T, Moenke G, Spahn CM, Lundmark R, Daumke O, Langen R Structure. 2014 Feb 4. pii: S0969-2126(14)00007-0. doi:, 10.1016/j.str.2013.12.015. PMID:24508342[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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