New progress has been made in the study of CNG gate-controlled molecular system

in the nucleotide gate-controlled ion channel (CNG) gene, certain disease-causing mutations are the direct cause of blindness and color blindness. To this end, Li Guohui, a researcher at the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences (hereinafter referred to as Dalian Chemical Institute), worked with a team of Columbia University professors Yang Jian and Asim Frank to make new progress in the field of interpretation of CNG's gate-controlled molecular machinery, the results of which were published online June 1 in Nature-Structural and Molecular Biology.
CNG ion channels are mainly distributed in the central nervous system of higher vertebrates and are closely related to visual and olfactory nerve sensing. Zhang Yuebin, one of the authors of the paper and an associate researcher at Dalian Chemical Institute, told the China Science Journal, "The study of the gateing system of CNG ion channels is of great significance for understanding the relevant pathogenicity and biological processes."
it is known that in visual cells, photoreactivation of photochrome reduces the concentration of cGMP mating in cells, causing the CNG channel to close and the cell membrane to produce superpolarization. In olfactory neurons, the activation of olfactory receptors by odor molecules increases the concentration of camp mats in cells, causing the CNG ion channel to open and depolarizing the cell membrane.
Previous research views that the key gated amino acids of CNG ion channels are E379 located in the extracellulation region of the protein, Li Guohui team found through theoretical simulations in the early stage, CNG ion channels really play a gate-controlled role of the key amino acids located in the CNG ion channel S6 spiral F403 and V407.theoretical calculations still need to be tested. In 2017, Li Guohui's team began seeking experimental collaboration to further demonstrate the new findings of the team's theoretical research.
through multiple inquiries, Li Guohui and Yang Jian and Asim Frank contacted. "Previously, I didn't know Yang Jian and Asim Frank, and our communication was mainly through email and WeChat." "A never-before-seen international cooperation began, " Mr. Li recalls.
Yang Jian has been involved in the relevant research, and through atomic resolution cryoscopy technology for the first time revealed the beautiful worm's CNG ion channel TMAX-4 full-length structure, the structure was analyzed and found to be in an open state when combined with cGMP ligation. Asim Frank is also one of the winners of the 2017 Nobel Prize in Chemistry and is known for inventing single-particle frozen electric mirrors.
the results of the two professors" team confirm that our theoretical calculations are correct. Zhang Yuebin said, "However, the process in the middle is not plain sailing, because the other side started the experimental feedback is that we may not be predicting the state of the right." "
" I had thought it might be an unsuccessful international cooperation, and was ready to give up. Li Guohui remembers receiving Yang Jian's WeChat again before and after the Spring Festival in 2019 was a bit of a surprise, Yang Jian said in WeChat: "We did structural experiments, and your prediction is basically the same." "
" did not expect that two years later, this cooperation can be restarted. "That's the charm of scientific research, " sighed Li Guohui.
Yang Jian and Asim Frank team analyzed the high-resolution 3D structure under CNG channel open state, closed state and F403/V407 double mutation, respectively, through single-particle frozen electron microscope technology, and confirmed the core role of F403 and V407 dual traps in regulating CNG channel ion transmission through electrophysiological experiments.
results provide new understanding of the molecular basis of the gate-controlled structure of CNG ion channels, which will be used in the future to develop drugs for the treatment of neurological disorders. (Source: Shen Chunlei, China Science Journal)
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