West Lake University published the latest Nature article, deciphering the CatSper channel body of the sperm activation switch

At around 23:00 on July 5th, the Wu Jianping team from the School of Life Sciences of West Lake University and West Lake Laboratory published in Nature online the latest research results titled "Structure of a mammalian sperm cation channel complex", reporting the key ion channel complex during fertilization.

This is the first time in the world to reveal the appearance of this super complex, and identify a number of previously undiscovered components, collectively referred to as "CatSper channel body" (CatSpermasome)

Shi Yigong, a structural biologist and president of West Lake University, commented: "This is a breakthrough that fully demonstrates the charm of structural biology

What is CatSper? What does it mean for our life activities? This needs to start from the origin of life-fertilization

Fertilization is the first step in the sexual reproduction of all higher organisms

Although the current assisted reproductive technology has been widely used, the research on the mechanism of the fertilization process is not deep enough.

CatSper, the full name of The cation channel of sperm, is a cation channel complex distributed on sperm, and is currently recognized as the most important calcium ion channel on the sperm cell membrane

In mouse models, the inactivation of CatSper can cause abnormal sperm motility and male sterility

To put it more vividly, if you want to be fertilized successfully, sperm needs to complete two very important things: "swim" to the egg and "drill" in the egg.

Therefore, CatSper has always been an important target for the treatment of male infertility and the development of new non-hormonal contraceptives.

However, in the past 20 years, although many research groups at home and abroad focused on the structural research of CatSper, the progress was extremely limited

"Ion channels are usually composed of a core component responsible for the transport of ions.

In 2019, Jianping Wu completed his postdoctoral research work from Princeton University and joined West Lake University full-time

When studying a protein in traditional structural biology, the main method is to introduce its gene into the cell and express the protein in the cell

After experiencing the previous failures, Wu Jianping's team realized that CatSper may have more potential active ingredients, and their lack made it impossible to obtain a complete CatSper protein

"Equivalent to the traditional method is to use cells to replicate CatSper, and we get ready-made CatSper directly from mouse sperm

Later, relying on the cryo-electron microscope platform of West Lake University, they used single-particle 3D reconstruction technology to analyze the 3D structure with a resolution of 2.
9 Å, and the true face of CatSper was finally presented
.

The structure shows that this is actually a super complex with at least 14 components, and Wu Jianping's team named it CatSpermasome (CatSpermasome)
.

The high-definition electron microscope three-dimensional reconstruction image shows that the components of the CatSper channel body overlap and surround, like a jellyfish, with a big "head" exposed outside the sperm cell membrane, the waist part is inserted in the middle of the cell membrane, and there are several thin " The legs" penetrate deep into the cells
.

Importantly, the research team discovered that one of the new functional components of the CatSper channel body is a major member of the transporter family
.

The traditional concept believes that ion channels are responsible for the transport of ions and transport proteins are responsible for the transport of small molecules.
Although the two are both cell membrane proteins, they are not related to each other
.
The CatSper channel body contains both channel proteins and transport proteins
.
This not only refreshes people's understanding of the composition of CatSper, but also subverts the traditional concept of ion channels and transporters fighting each other in the cell
.

This work reveals for the first time the unique assembly method of the CatSper channel body, provides an in-depth mechanism explanation for the understanding of its functional regulation, ion transport and other processes, and provides subsequent infertility-related drugs and non-hormonal contraceptives based on the structure of the CatSper channel body.
The development has laid an important foundation
.

West Lake University is the communication unit for this paper
.
Wu Jianping, a distinguished researcher of the School of Life Sciences, is the corresponding author of the paper, West Lake University doctoral student Lin Shiyi and postdoctoral student Ke Meng are the co-first authors of the paper, and doctoral student Zhang Yuqi is the second author of the paper
.
Yan Zhen, a distinguished researcher of West Lake University, has made important contributions to this article
.
In addition, this research was strongly supported by the cryo-electron microscopy platform of West Lake University, the High-performance Computing Center of West Lake University, the Mass Spectrometry and Metabolism Platform of West Lake University, and the Laboratory Animal Center of West Lake University
.
This work was supported by the West Lake Education Foundation and West Lake Laboratory
.

Original link:

https:// to Wu Jianping Laboratory]

Wu Jianping, a distinguished researcher of the School of Life Sciences, West Lake University, is engaged in the research on the structure and function of ion channels and transporters related to transmembrane transport, and has achieved many important scientific research results.
He has published many research articles in the top international academic journals Cell, Nature, Science, etc.
The number of citations exceeded 3000 times
.
In 2019, Wu Jianping established a biological structure laboratory at West Lake University, which mainly combined structural biology, electrophysiology, biochemistry and other methods to explore the mechanism of fertilization, an important life process
.
These studies will provide new ideas for the diagnosis, treatment and drug development of related diseases such as infertility
.
Wu Jianping's laboratory has long-term recruited post-doctoral students, doctoral students and research assistants who have backgrounds in structural biology, reproductive biology, biochemistry, cryo-electron microscopy data processing methods, or are interested in them.
Welcome to join!

Email: wujianping@westlake.
edu.
cn