Structure of a mammalian sperm cation channel complex

• Published in: Nature (London) Vol. 595; no. 7869; pp. 746 - 750
• Main Authors: Lin, Shiyi, Ke, Meng, Zhang, Yuqi, Yan, Zhen, Wu, Jianping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.07.2021; Nature Publishing Group
• Subjects: 101/28; 101/58; 45/23; 45/29; 45/77; 631/443/494; 631/535/1258/1259; 631/57/2283; 64/60; 82/16; 82/29; 82/83; Animals; Calcium Channels - chemistry; Cations; Cell research; Cells; Contraceptives; Cryoelectron Microscopy; Domains; Electron microscopy; Fertility; Health aspects; Humanities and Social Sciences; Infertility; Ion channels; Ion Channels - chemistry; Ions; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motility; multidisciplinary; Mutation; Physiological aspects; Physiology; Pore formation; Pore-forming proteins; Protein Structure, Quaternary; Proteins; Science; Science (multidisciplinary); Seminal Plasma Proteins - chemistry; Sperm; Sperm Motility; Spermatozoa; Structure; China
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-021-03742-6

The cation channel of sperm (CatSper) is essential for sperm motility and fertility 1 , 2 . CatSper comprises the pore-forming proteins CATSPER1–4 and multiple auxiliary subunits, including CATSPERβ, γ, δ, ε, ζ, and EFCAB9 1 , 3 – 9 . Here we report the cryo-electron microscopy (cryo-EM) structure of the CatSper complex isolated from mouse sperm. In the extracellular view, CATSPER1–4 conform to the conventional domain-swapped voltage-gated ion channel fold 10 , following a counterclockwise arrangement. The auxiliary subunits CATSPERβ, γ, δ and ε—each of which contains a single transmembrane segment and a large extracellular domain—constitute a pavilion-like structure that stabilizes the entire complex through interactions with CATSPER4, 1, 3 and 2, respectively. Our EM map reveals several previously uncharacterized components, exemplified by the organic anion transporter SLCO6C1. We name this channel–transporter ultracomplex the CatSpermasome. The assembly and organization details of the CatSpermasome presented here lay the foundation for the development of CatSpermasome-related treatments for male infertility and non-hormonal contraceptives. A structure of the sperm-specific CatSper complex features a number of additional components; together, these components and the CatSper complex are termed the CatSpermasome.