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.
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http://dx.doi.org/10.1016/j.str.2013.12.015 | DOI Listing |
Emerg Microbes Infect
December 2024
One Health Laboratory, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People's Republic of China.
African swine fever virus (ASFV) causes highly contagious swine disease, African swine fever (ASF), thereby posing a severe socioeconomic threat to the global pig industry and underscoring that effective antiviral therapies are urgently required. To identify safe and efficient anti-ASFV compounds, a natural compound library was screened by performing an established cell-based ELISA in an ASFV-infected porcine alveolar macrophage (PAM) model. In total, 6 effective anti-ASFV compounds with low cytotoxicity were identified.
View Article and Find Full Text PDFNat Commun
November 2024
Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these conditions. Here, we show in male mice in vivo that the adipocyte plasma membrane undergoes caveolar domain reorganization upon lipid droplet expansion.
View Article and Find Full Text PDFHum Genet
August 2024
Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
Theor Appl Genet
June 2024
China National Center for Rice Improvement and State Key Laboratory of Rice Biology and Breeding, China National Rice Research Institute, Hangzhou, 311400, China.
OsCOL5, an ortholog of Arabidopsis COL5, is involved in photoperiodic flowering and enhances rice yield through modulation of Ghd7 and Ehd2 and interactions with OsELF3-1 and OsELF3-2. Heading date, also known as flowering time, plays a crucial role in determining the adaptability and yield potential of rice (Oryza sativa L.).
View Article and Find Full Text PDFCurr Opin Cell Biol
June 2024
Medical and Translational Biology, Umeå University, 901 87, Umeå, Sweden.
Caveolae are atypical plasma membrane invaginations that take part in lipid sorting and regulation of oxidative and mechanical plasma membrane stress. Caveola formation requires caveolin, cavin, and specific lipid types. The recent advances in understanding the structure and assembly of caveolin and cavin complexes within the membrane context have clarified the fundamental processes underlying caveola biogenesis.
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