| Structural highlights
Function
HAP2_CHLRE During fertilization, required on male (minus) gametes for their fusion with female (plus) gametes (PubMed:18367645, PubMed:20335357, PubMed:25655701, PubMed:28235200). Required for membrane fusion, but not for the initial adhesion between gametes (PubMed:18367645, PubMed:25655701, PubMed:28235200). Inserts (via its extracellular domain) into lipid membranes (in vitro) (PubMed:28235200). Probably initiates the fusion of gamete cell membranes by inserting its extracellular domain into the cell membrane of a female gamete (PubMed:28235200).[1] [2] [3] [4]
Publication Abstract from PubMed
Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and protists (including important human pathogens like Plasmodium)-suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life.
The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.,Fedry J, Liu Y, Pehau-Arnaudet G, Pei J, Li W, Tortorici MA, Traincard F, Meola A, Bricogne G, Grishin NV, Snell WJ, Rey FA, Krey T Cell. 2017 Feb 23;168(5):904-915.e10. doi: 10.1016/j.cell.2017.01.024. PMID:28235200[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu Y, Tewari R, Ning J, Blagborough AM, Garbom S, Pei J, Grishin NV, Steele RE, Sinden RE, Snell WJ, Billker O. The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes. Genes Dev. 2008 Apr 15;22(8):1051-68. doi: 10.1101/gad.1656508. Epub 2008 Mar 26. PMID:18367645 doi:http://dx.doi.org/10.1101/gad.1656508
- ↑ Liu Y, Misamore MJ, Snell WJ. Membrane fusion triggers rapid degradation of two gamete-specific, fusion-essential proteins in a membrane block to polygamy in Chlamydomonas. Development. 2010 May;137(9):1473-81. doi: 10.1242/dev.044743. Epub 2010 Mar 24. PMID:20335357 doi:http://dx.doi.org/10.1242/dev.044743
- ↑ Liu Y, Pei J, Grishin N, Snell WJ. The cytoplasmic domain of the gamete membrane fusion protein HAP2 targets the protein to the fusion site in Chlamydomonas and regulates the fusion reaction. Development. 2015 Mar 1;142(5):962-71. doi: 10.1242/dev.118844. Epub 2015 Feb 5. PMID:25655701 doi:http://dx.doi.org/10.1242/dev.118844
- ↑ Fedry J, Liu Y, Pehau-Arnaudet G, Pei J, Li W, Tortorici MA, Traincard F, Meola A, Bricogne G, Grishin NV, Snell WJ, Rey FA, Krey T. The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. Cell. 2017 Feb 23;168(5):904-915.e10. doi: 10.1016/j.cell.2017.01.024. PMID:28235200 doi:http://dx.doi.org/10.1016/j.cell.2017.01.024
- ↑ Fedry J, Liu Y, Pehau-Arnaudet G, Pei J, Li W, Tortorici MA, Traincard F, Meola A, Bricogne G, Grishin NV, Snell WJ, Rey FA, Krey T. The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. Cell. 2017 Feb 23;168(5):904-915.e10. doi: 10.1016/j.cell.2017.01.024. PMID:28235200 doi:http://dx.doi.org/10.1016/j.cell.2017.01.024
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