Structural highlights
FunctionSACA6_HUMAN Sperm protein required for fusion of sperm with the egg membrane during fertilization (By similarity). May regulate the expression of sperm surface protein DCST2 (By similarity).[UniProtKB:A0A8M9PDM1][UniProtKB:E9Q8Q8] Publication Abstract from PubMedSPACA6 is a sperm-expressed surface protein that is critical for gamete fusion during mammalian sexual reproduction. Despite this fundamental role, little is known about how SPACA6 specifically functions. We elucidated the crystal structure of the SPACA6 ectodomain at 2.2-A resolution, revealing a two-domain protein containing a four-helix bundle and Ig-like beta-sandwich connected via a quasi-flexible linker. This structure is reminiscent of IZUMO1, another gamete fusion-associated protein, making SPACA6 and IZUMO1 founding members of a superfamily of fertilization-associated proteins, herein dubbed the IST superfamily. The IST superfamily is defined structurally by its distorted four-helix bundle and a pair of disulfide-bonded CXXC motifs. A structure-based search of the AlphaFold human proteome identified more protein members to this superfamily; remarkably, many of these proteins are linked to gamete fusion. The SPACA6 structure and its connection to other IST-superfamily members provide a missing link in our knowledge of mammalian gamete fusion. SPACA6 ectodomain structure reveals a conserved superfamily of gamete fusion-associated proteins.,Vance TDR, Yip P, Jimenez E, Li S, Gawol D, Byrnes J, Uson I, Ziyyat A, Lee JE Commun Biol. 2022 Sep 17;5(1):984. doi: 10.1038/s42003-022-03883-y. PMID:36115925[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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