EMD-2532
Tomographic subvolume average of EFF-1 fusogen on extracellular vesicles
EMD-2532
Subtomogram averaging45.0 Å
Deposition: 17/12/2013Map released: 27/08/2014
Last modified: 09/03/2016
Sample Organism:
Caenorhabditis elegans
Sample: Epithelial fusion failure 1 (EFF-1) Isoform A on extracellular vesicles
Deposition Authors: Zeev-Ben-Mordehai T, Vasishtan D, Siebert CA, Grunewald K
Sample: Epithelial fusion failure 1 (EFF-1) Isoform A on extracellular vesicles
Deposition Authors: Zeev-Ben-Mordehai T, Vasishtan D, Siebert CA, Grunewald K
The full-length cell-cell fusogen EFF-1 is monomeric and upright on the membrane.
Zeev-Ben-Mordehai T Vasishtan D Siebert CA Gruenewald K
(2014) Nat Commun , 5 , 3912 - 3912
(2014) Nat Commun , 5 , 3912 - 3912
Abstract:
Fusogens are membrane proteins that remodel lipid bilayers to facilitate membrane merging. Although several fusogen ectodomain structures have been solved, structural information on full-length, natively membrane-anchored fusogens is scarce. Here we present the electron cryo microscopy three-dimensional reconstruction of the Caenorhabditis elegans epithelial fusion failure 1 (EFF-1) protein natively anchored in cell-derived membrane vesicles. This reveals a membrane protruding, asymmetric, elongated monomer. Flexible fitting of a protomer of the EFF-1 crystal structure, which is homologous to viral class-II fusion proteins, shows that EFF-1 has a hairpin monomeric conformation before fusion. These structural insights, when combined with our observations of membrane-merging intermediates between vesicles, enable us to propose a model for EFF-1 mediated fusion. This process, involving identical proteins on both membranes to be fused, follows a mechanism that shares features of SNARE-mediated fusion while using the structural building blocks of the unilaterally acting class-II viral fusion proteins.
Fusogens are membrane proteins that remodel lipid bilayers to facilitate membrane merging. Although several fusogen ectodomain structures have been solved, structural information on full-length, natively membrane-anchored fusogens is scarce. Here we present the electron cryo microscopy three-dimensional reconstruction of the Caenorhabditis elegans epithelial fusion failure 1 (EFF-1) protein natively anchored in cell-derived membrane vesicles. This reveals a membrane protruding, asymmetric, elongated monomer. Flexible fitting of a protomer of the EFF-1 crystal structure, which is homologous to viral class-II fusion proteins, shows that EFF-1 has a hairpin monomeric conformation before fusion. These structural insights, when combined with our observations of membrane-merging intermediates between vesicles, enable us to propose a model for EFF-1 mediated fusion. This process, involving identical proteins on both membranes to be fused, follows a mechanism that shares features of SNARE-mediated fusion while using the structural building blocks of the unilaterally acting class-II viral fusion proteins.