Structure of a mammalian sperm cation channel complex

The cation channel of sperm (CatSper) is essential for sperm motility and fertility.sup.1,2. CatSper comprises the pore-forming proteins CATSPER1-4 and multiple auxiliary subunits, including CATSPER[beta], [gamma], [delta], [epsilon], [zeta], and EFCAB9.sup.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.sup.10, following a counterclockwise arrangement. The auxiliary subunits CATSPER[beta], [gamma], [delta] and [epsilon]--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.
Author(s): Shiyi Lin [sup.1] [sup.2] [sup.3] , Meng Ke [sup.1] [sup.2] [sup.3] , Yuqi Zhang [sup.1] [sup.2] [sup.3] , Zhen Yan [sup.1] [sup.2] [sup.3] , Jianping Wu [sup.1] [sup.2] [sup.3] [...]