Molecular determinants of species-specific cell-cell recognition activating the class II gamete fusogen HAP2

Species-specific adhesion of complementary gametes is a prerequisite to cell fusion during fertilization. Despite its importance, the molecular mechanism underlying cell-cell recognition and membrane adhesion to drive gamete fusion is not fully understood for any organism. In the alga, Chlamydomonas, the species-specific gamete adhesion protein MAR1 guides the fusogen HAP2 into a pre-fusion conformation on mt- gametes and serves as a receptor for the FUS1 adhesion protein on mt+ gametes. Here, we show that soluble recombinant MAR1 completely blocks the HAP2-dependent gamete fusion process by binding to FUS1 on mt+ gametes and report the X-ray structure of the MAR1-FUS1 complex. In vivo gamete fusion experiments showed that mutations of key residues at the observed MAR1-FUS1 interface strongly impair adhesion, yet gamete fusion still proceeds, highlighting the efficiency of the fusion-activation process. These findings uncover the molecular architecture of a surface receptor complex whose formation releases the viral class II viral fusion-protein ortholog HAP2, allowing it to undergo its membrane-fusogenic conformational change.