On July 5, 2021, Dr. Jianping Wu’s team from the School of Life Sciencesand the Westlake Laboratory of Life Sciences and Biomedicine at Westlake University published their latest research online in Nature entitled “Structure of a Mammalian Sperm Cation Channel Complex”. The research reports a high-resolution three-dimensional structure of CatSper, the key cation channel complex for sperm fertilization.

This is the first time in the world that researchers have revealed the appearance of this super complex. Moreover, the team have identified a number of previously uncharacterized components of CatSper, collectively referred to as CatSpermasome.

Yigong Shi, a distinguished structural biologist, commented highly on the study, “This is a great breakthrough that fully demonstrates the charm of structural biology. As a result of this research, we can now for the first time see the full picture of CatSper, a calcium ion channel complex that plays a key role in the fertilization process of mammals. More importantly, identification of new protein components, and the concept of CatSpermasome will greatly promote research into its function.”

Fertilization is a fundamental biological process that seeds a new life. However, mechanistic understanding of fertilization is quite limited. There remain many biological questions in this field that need to be solved urgently. Research on the structure and function of the sperm activation switch CatSper is one of them.

CatSper is a cation channel complex that is essential for sperm motility and fertility. It has been recognized as the most important calcium channel on the sperm flagellum. Mutations in CatSper impair male fertility. As such, CatSper has always been important target for the treatment of male infertility and the development of novel non-hormonal contraceptives. Therefore, determination of the high-resolution structure of CatSper is of great significance.

CatSper contains the largest number of subunits on any known ion channel. The expression and purification of CatSper has been proved extremely difficult. Dr. Wu’s team solve this problem through an elegant endogenous purification strategy. Using single-particle cryo-EM technology, they finally solve the 3D structure of CatSper with an overall resolution of 2.9 Å. The true face of CatSper finally appeared after two decades since it was identified.

This work reveals the unique assembly of the CatSper channel complex, providing an in-depth mechanistic understanding of its function, ion selection, voltage sensing and gating process. More excitingly, the structure has identified several previously uncharacterized components exemplified by an organic anion transporter. Thus, CatSper is a channel-transporter super complex, which Dr. Wu's team named the CatSpermasome. This study not only opens up many new directions and opportunity for future functional studies on CatSper, but also has provided an important foundation for the development of CatSpermasome-related treatment for male infertility and non-hormonal contraceptives.

To learn more about this important breakthrough read the full article at nature: https://www.nature.com/articles/s41586-021-03742-6

[About Dr. Jianping Wu]

Dr. Jianping Wu is engaged in research on the structure and function of ion channels and transporters related to transmembrane transport. He has achieved a number of important scientific results, with over 3000 citations of his work. In 2019, Jianping Wu established a laboratory with the Westlake University School of Life Sciences which mainly combines structural biology, electrophysiology, biochemistry and other methods to explore the mechanisms of important membrane proteins involved in fertilization. These studies will provide new ideas for the diagnosis, treatment and drug development of infertility and other related diseases. Jianping Wu's laboratory has been recruiting talented post-doctoral fellows, doctoral students, and research assistants with backgrounds in structural biology, reproductive biology, electrophysiology and biochemistry. If this is an area of interest for you, we hope you will join us! Email: wujianping@westlake.edu.cn