Structural basis of eukaryotic cell-cell fusion.

Area of Science:

• Molecular Biology
• Structural Biology
• Developmental Biology

Background:

• Cell-cell fusion is a fundamental biological process critical for development and tissue formation.
• Viral fusion proteins mediate membrane merging, a process essential for viral entry.
• The C. elegans EFF-1 protein is a key mediator of developmental cell-cell fusion.

Purpose of the Study:

• To elucidate the structural basis of EFF-1-mediated cell-cell fusion.
• To compare the structure of EFF-1 with known viral fusion proteins.
• To understand the mechanism by which EFF-1 drives membrane fusion.

Main Methods:

• X-ray crystallography to determine the 2.6 Å crystal structure of the EFF-1 trimer.
• Structural comparison with viral class II fusion proteins.
• Functional assays to assess the role of EFF-1 trimerization in cell fusion.

Main Results:

• The EFF-1 trimer exhibits structural homology to postfusion class II viral fusion proteins.
• EFF-1 lacks a nonpolar fusion loop characteristic of viral fusion proteins.
• Blocking EFF-1 trimerization inhibits the cell fusion process.

Conclusions:

• EFF-1 utilizes a distinct mechanism for cell-cell fusion compared to viral fusion proteins.
• Cell fusion mediated by EFF-1 involves trans-trimerization, bringing transmembrane segments of opposing membranes into contact.
• This mechanism is analogous to SNARE-mediated vesicle fusion, facilitating membrane merging.