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

Pinello, J. F.; Ferrino, A.; Hussain, H.; Legrand, P.; Manikumar, S.; Demissie, R.; Rey, F. A.; Snell, W. J.; Baquero, E.

doi:10.1101/2025.05.09.653094

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bioRxiv · 10.1101/2025.05.09.653094

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

Pinello, J. F.·Ferrino, A.·Hussain, H.·Legrand, P.·Manikumar, S.·Demissie, R.·Rey, F. A.·Snell, W. J.·Baquero, E.

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Abstract

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.

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Pinello, J. F., Ferrino, A., Hussain, H., Legrand, P., Manikumar, S., Demissie, R., Rey, F. A., Snell, W. J., Baquero, E.. 2025-05-13. Molecular determinants of species-specific cell-cell recognition activating the class II gamete fusogen HAP2. https://doi.org/10.1101/2025.05.09.653094

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