First Author | Lin S | Year | 2021 |
Journal | Nature | Volume | 595 |
Issue | 7869 | Pages | 746-750 |
PubMed ID | 34225353 | Mgi Jnum | J:314092 |
Mgi Id | MGI:6810805 | Doi | 10.1038/s41586-021-03742-6 |
Citation | Lin S, et al. (2021) Structure of a mammalian sperm cation channel complex. Nature 595(7869):746-750 |
abstractText | 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 CATSPERbeta, gamma, delta, epsilon, zeta, 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 CATSPERbeta, 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. |