The world's most powerful X-ray laser Gong Gong: crack cell signaling password

The cross-team led by Xu Huaqiang, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, has successfully solved the crystal structure of phosphorylated Rhodopsin and Arrestin complexes and cracked the phosphoric acid responsible for turning off GPCR signaling The password. July 27, related research results published in the cover article in the "cell" magazine.

The function of life relies on the signaling password to embody or execute. G protein-coupled receptors (GPCRs), the largest family of cell membrane surface receptors in the human body, take on the role of "signal soldiers" for cell signaling through two major signaling pathways, G-protein and repressor proteins. When stimulated by external signals, GPCR activates the G protein to signal an "open" signal. The "off" signal, then, comes from the phosphorylation code - once the phosphorylated GPCR tail is activated, the repressor activates and binds tightly to the complex, shutting down the signaling. Therefore, identifying and interpreting GPCR phosphorylation codes is an important scientific issue in the field of cell signaling today.

It is reported that Xu Huaqiang led by the cross-team in 2015 successfully parse GPCR and repressor complexes based on the complete complex structure of the structure of the rear of the high-resolution structure and phosphorylation mechanism to tackle.

"We used the most powerful X-ray laser in the world to see the tail structure information of the composite crystal and to analyze the process of its tail phosphorylation recruiting and binding to the repressor protein." Xu Huaqiang compared the research process to the life-password layer "To verify the universality of phosphorylation codes, we tested 96% of the GPCR proteins and found that 70% -80% of the GPCR's" shut down "signals are controlled by phosphorylation codes." Finally, a series of validation biology Functional verification, GPCR recruits the phosphorylation code for the repressor protein to crack - GPCR recruits and binds to the repressor protein through phosphorylation of its tail amino acids, and is found to be ubiquitous across the GPCR proteome.

It is understood that a major breakthrough in structural biology is often closely related to the combination of synchrotron radiation source + X-ray free electron laser. At present, there are six such combinations in the world, which are located in Germany, the United States, Japan, South Korea, Switzerland and Italy. "We are very much looking forward to China's own major science and technology infrastructure, such as soft X-ray and hard X-ray free electron laser devices under construction and promotion." Xu Huaqiang said: "These large science platforms can provide scientists with more advanced and rich Comprehensive experimental means. "

According to reports, the study was funded by the state's "major new drug creation" major projects, 973, pilot projects, and international projects. Cooperative research institutions include the University of Toronto, Scripps Research Institute, Germany Desy Free Electron Laser Science Center, Hamburg, Germany Ultrafast Imaging Center, University of California, Los Angeles, University of Southern California, Shanghai University of Science and Vanderbilt University and so on.


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