Species-specific gamete recognition initiates fusion-driving trimer formation by conserved fusogen HAP2

Jun Zhang, Jennifer F. Pinello, Ignacio Fernández, Eduard Baquero, Juliette Fedry, Félix A. Rey, William J. Snell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Recognition and fusion between gametes during fertilization is an ancient process. Protein HAP2, recognized as the primordial eukaryotic gamete fusogen, is a structural homolog of viral class II fusion proteins. The mechanisms that regulate HAP2 function, and whether virus-fusion-like conformational changes are involved, however, have not been investigated. We report here that fusion between plus and minus gametes of the green alga Chlamydomonas indeed requires an obligate conformational rearrangement of HAP2 on minus gametes from a labile, prefusion form into the stable homotrimers observed in structural studies. Activation of HAP2 to undergo its fusogenic conformational change occurs only upon species-specific adhesion between the two gamete membranes. Following a molecular mechanism akin to fusion of enveloped viruses, the membrane insertion capacity of the fusion loop is required to couple formation of trimers to gamete fusion. Thus, species-specific membrane attachment is the gateway to fusion-driving HAP2 rearrangement into stable trimers.

Original languageEnglish (US)
Article number4380
JournalNature communications
Issue number1
StatePublished - Dec 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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