4CID

Structural insights into the N-terminus of the EHD2 ATPase

Summary for 4CID

• Entry DOI: 10.2210/pdb4cid/pdb
• Descriptor: EH DOMAIN-CONTAINING PROTEIN 2, CALCIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: hydrolase, mechanochemical atpase, dynamin superfamily
• Biological source: MUS MUSCULUS (HOUSE MOUSE)
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q8BH64
• Total number of polymer chains: 1
• Total formula weight: 63212.85

Authors

Shah, C.,Daumke, O. (deposition date: 2013-12-06, release date: 2014-02-19, Last modification date: 2024-11-13)

Primary citation

Shah, C.,Hegde, B.G.,Mor, B.,Behrmann, E.,Mielke, T.,Moenke, G.,Spahn, C.M.,Lundmark, R.,Daumke, O.,Langen, R.
Structural Insights Into Membrane Interaction and Caveolar Targeting of Dynamin-Like Ehd2.
Structure, 22:409-, 2014

PubMed 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.

PubMed: 24508342
DOI: 10.1016/J.STR.2013.12.015

Experimental method

X-RAY DIFFRACTION (3 Å)