Molecular determinants of species-specific gamete adhesion triggering HAP2-mediated membrane fusion

Species-specific adhesion of gametes is a prerequisite to cell fusion during fertilization, yet the underlying molecular mechanisms are not fully understood for any organism. In Chlamydomonas, the adhesion protein MAR1 chaperones the conserved fusogen HAP2 into a pre-fusion conformation on the mt− gamete and is the receptor for the adhesion protein FUS1 on the mt+ gamete. Here, we report the X-ray structure of the FUS1/MAR1 adhesion complex, showing that it forms a (FUS1/MAR1)2 dimer. We found that mutagenesis at the observed MAR1-FUS1 interface strongly impairs adhesion, and that recombinant, soluble MAR1 binds to FUS1 on activated mt+ gametes and completely blocks HAP2 triggering for fusion. These findings uncover the molecular architecture of a cell surface receptor complex whose formation is required to trigger the membrane-fusogenic conformational change of a eukaryotic class II membrane fusion protein. The molecular mechanisms linking gamete adhesion to membrane fusion are unknown. Here, the authors report the crystal structure of the complex between Chlamydomonas gamete adhesion proteins MAR1 and FUS1 and show that complex formation triggers fusogenic reconfiguration of conserved gamete fusion protein HAP2.