TY - JOUR
T1 - Structural basis of eukaryotic cell-cell fusion
AU - Pérez-Vargas, Jimena
AU - Krey, Thomas
AU - Valansi, Clari
AU - Avinoam, Ori
AU - Haouz, Ahmed
AU - Jamin, Marc
AU - Raveh-Barak, Hadas
AU - Benjamin, Podbilewicz
AU - Rey, Félix A.
N1 - Funding Information: F.A.R. was funded by the French “Agence Nationale pour la Recherche” grant ANR-2010-BLAN-1211 01 and by Institut Pasteur, CNRS, and Merck-Serono. B.P. was funded by the ERC Advanced grant 268843 and the Israel Science Foundation (ISF grants 1542/07 and 826/08). B.P. was a Grass fellow at Radcliffe Institute for Advanced Study, Harvard University. We thank Patrick England, Bertrand Raynal, and Patrick Weber of the Pasteur Proteopole for technical help; the staff of synchrotron beamlines PX-I at the Swiss Light Source, Proxima-1 at SOLEIL, and ID23-1 at the European Synchrotron Radiation Facility for help during data collection; Clemens Vonrhein and Gerard Bricogne from Global Phasing Ltd. for methodological concepts; Tom Rapoport and his lab for discussions and for hosting B.P. at Harvard Medical School; and Jorge Verdin Ramos from Technion and the members of the Rey and Podbilewicz labs for discussions.
PY - 2014/4/10
Y1 - 2014/4/10
N2 - Cell-cell fusion proteins are essential in development. Here we show that the C. elegans cell-cell fusion protein EFF-1 is structurally homologous to viral class II fusion proteins. The 2.6 Å crystal structure of the EFF-1 trimer displays the same 3D fold and quaternary conformation of postfusion class II viral fusion proteins, although it lacks a nonpolar "fusion loop," indicating that it does not insert into the target membrane. EFF-1 was previously shown to be required in both cells for fusion, and we show that blocking EFF-1 trimerization blocks the fusion reaction. Together, these data suggest that whereas membrane fusion driven by viral proteins entails leveraging of a nonpolar loop, EFF-1-driven fusion of cells entails trans-trimerization such that transmembrane segments anchored in the two opposing membranes are brought into contact at the tip of the EFF-1 trimer to then, analogous to SNARE-mediated vesicle fusion, zip the two membranes into one.
AB - Cell-cell fusion proteins are essential in development. Here we show that the C. elegans cell-cell fusion protein EFF-1 is structurally homologous to viral class II fusion proteins. The 2.6 Å crystal structure of the EFF-1 trimer displays the same 3D fold and quaternary conformation of postfusion class II viral fusion proteins, although it lacks a nonpolar "fusion loop," indicating that it does not insert into the target membrane. EFF-1 was previously shown to be required in both cells for fusion, and we show that blocking EFF-1 trimerization blocks the fusion reaction. Together, these data suggest that whereas membrane fusion driven by viral proteins entails leveraging of a nonpolar loop, EFF-1-driven fusion of cells entails trans-trimerization such that transmembrane segments anchored in the two opposing membranes are brought into contact at the tip of the EFF-1 trimer to then, analogous to SNARE-mediated vesicle fusion, zip the two membranes into one.
UR - http://www.scopus.com/inward/record.url?scp=84898627805&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.02.020
DO - 10.1016/j.cell.2014.02.020
M3 - مقالة
SN - 0092-8674
VL - 157
SP - 407
EP - 419
JO - Cell
JF - Cell
IS - 2
ER -