Structural basis of eukaryotic cell-cell fusion

Jimena Pérez-Vargas, Thomas Krey, Clari Valansi, Ori Avinoam, Ahmed Haouz, Marc Jamin, Hadas Raveh-Barak, Benjamin Podbilewicz*, Félix A. Rey

*Corresponding author for this work
108 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalCell
Volume157
Issue number2
Pages (from-to)407-419
Number of pages13
ISSN0092-8674
DOIs
Publication statusPublished - 10.04.2014

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