{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPACA6 is a sperm surface protein that plays a critical role in mammete fusion during fertilization. Functional studies have shown that its absence in male mice leads to infertility, with sperm accumulating in the perivitelline space and failing to fuse with the oocyte. Moreover, human sperm retain SPACA6 in the equatorial segment after the acrosomal reaction, and inhibition of SPACA6 by specific antibodies impairs gamete fusion. These findings underscore the protein’s indispensable function in the adhesion/fusion process between gametes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary to its role in fusion, the structural elucidation of the SPACA6 ectodomain has revealed that the protein comprises two distinct domains: a distorted four‐helix bundle and an Ig-like β‐sandwich, connected by a quasi-flexible linker. This architecture mirrors that of IZUMO1, another key player in gamete fusion, thereby establishing SPACA6 and IZUMO1 as founding members of the IST superfamily, which is defined by its unique four-helix bundle structure and characteristic pairs of disulfide-bonded CXXC motifs. These structural insights not only explain the protein’s configuration but also hint at a broader superfamily of fertilization-associated proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, the functional and structural evidence suggests that SPACA6, in concert with IZUMO1, forms a critical molecular complex necessary for gamete fusion. Although their roles are non-redundant, their concomitant presence appears essential for the recruitment of other yet-to-be-identified fusogenic factors, which together orchestrate the intricate process of gamete adhesion and membrane fusion during mammalian fertilization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sandrine Barbaux, Côme Ialy-Radio, Myriam Chalbi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sperm SPACA6 protein is required for mammalian Sperm-Egg Adhesion/Fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-62091-y"}], "href": "https://doi.org/10.1038/s41598-020-62091-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32210282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32210282"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tyler D R Vance, Patrick Yip, Elisabet Jiménez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPACA6 ectodomain structure reveals a conserved superfamily of gamete fusion-associated proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-022-03883-y"}], "href": "https://doi.org/10.1038/s42003-022-03883-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36115925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36115925"}]}]}]}