SPACA6 ectodomain structure reveals a conserved superfamily of gamete fusion-associated proteins

• DOI: 10.1038/s42003-022-03883-y
• Publication Date: 2022-09-17T06:02:39Z
• Authors: Tyler D. R. Vance; Patrick Yip; Elisabet Jiménez; Sheng Li; Diana Gawol; James Byrnes; Isabel Usón; Ahmed Ziyyat; Jeffrey E. Lee
• Keywords: Ectodomain; Gamete; Proteome

Abstract SPACA6 is a sperm-expressed surface protein that critical for gamete fusion during mammalian sexual reproduction. Despite this fundamental role, little known about how specifically functions. We elucidated the crystal structure of ectodomain at 2.2-Å resolution, revealing two-domain containing four-helix bundle and Ig-like β-sandwich connected via quasi-flexible linker. This reminiscent IZUMO1, another fusion-associated protein, making IZUMO1 founding members superfamily fertilization-associated proteins, herein dubbed IST superfamily. The defined structurally by its distorted pair disulfide-bonded CXXC motifs. A structure-based search AlphaFold human proteome identified more to superfamily; remarkably, many these proteins are linked fusion. connection other IST-superfamily provide missing link in our knowledge