Format

Send to

Choose Destination
Structure. 2014 Mar 4;22(3):409-420. doi: 10.1016/j.str.2013.12.015. Epub 2014 Feb 6.

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

Author information

1
Max-Delbrück-Center for Molecular Medicine, Crystallography, Robert-Rössle-Straße 10, 13092 Berlin, Germany.
2
Institute of Chemistry and Biochemistry, Free University Berlin, Takustraße 6, 14195 Berlin, Germany.
3
Post Graduate Department of Physics, Rani Channamma University, Vidyasangama, Belagavi-591156, India.
4
Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
5
Institute of Medical Physics and Biophysics, Charité, Charitéplatz 1, 10117 Berlin, Germany.
6
UltraStrukturNetzwerk, Max-Planck-Institute for Molecular Genetics, Ihnestraße 73, 14195 Berlin.
7
Zilkha Neurogenetic Institute, University of Southern California, 1501 San Pablo Street, Los Angeles, CA 90033, USA.
#
Contributed equally

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.

PMID:
24508342
PMCID:
PMC3979964
DOI:
10.1016/j.str.2013.12.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center