| 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
HAP2 is a class II gamete fusogen in many eukaryotic kingdoms. A crystal structure of Chlamydomonas HAP2 shows a trimeric fusion state. Domains D1, D2.1 and D2.2 line the 3-fold axis; D3 and a stem pack against the outer surface. Surprisingly, hydrogen-deuterium exchange shows that surfaces of D1, D2.2 and D3 closest to the 3-fold axis are more dynamic than exposed surfaces. Three fusion helices in the fusion loops of each monomer expose hydrophobic residues at the trimer apex that are splayed from the 3-fold axis, leaving a solvent-filled cavity between the fusion loops in each monomer. At the base of the two fusion loops, Arg185 docks in a carbonyl cage. Comparisons to other structures, dynamics, and the greater effect on Chlamydomonas gamete fusion of mutation of axis-proximal than axis-distal fusion helices suggest that the apical portion of each monomer could tilt toward the 3-fold axis with merger of the fusion helices into a common fusion surface.
Fusion surface structure, function, and dynamics of gamete fusogen HAP2.,Feng J, Dong X, Pinello J, Zhang J, Lu C, Iacob RE, Engen JR, Snell WJ, Springer TA Elife. 2018 Oct 3;7. pii: 39772. doi: 10.7554/eLife.39772. PMID:30281023[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
- ↑ Feng J, Dong X, Pinello J, Zhang J, Lu C, Iacob RE, Engen JR, Snell WJ, Springer TA. Fusion surface structure, function, and dynamics of gamete fusogen HAP2. Elife. 2018 Oct 3;7. pii: 39772. doi: 10.7554/eLife.39772. PMID:30281023 doi:http://dx.doi.org/10.7554/eLife.39772
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