5mf1

Crystal structure of a C-terminally truncated trimeric ectodomain of the Chlamydomonas reinhardtii gamete fusion protein HAP2

spinqualitylabelsall models 5mf1, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mf1 is a 3 chain structure with sequence from Chlamydomonas reinhardtii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.3Å Ligands: NAG, NGA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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