The dopamine-like DRD1-Gs signal complex was parsed

zhang Lei, a professor in the School of Physics at Xi'an Jiao university, has made significant progress in the regulation of dopamine subjects using cryoelectric technology in collaboration with Sichuan University, Shandong University, National Protein Center (Shanghai), Hong Kong Chinese University, etc. Recently, the results of this study were published online in Cells with the title "The compound recognition and variant regulation of DRD1-Gs signal complex".
As a neurotransmitter that can make people feel good, dopamine plays an important role in the treatment of central nervous system diseases, regulating a variety of physiological processes such as addiction, memory, reward, metabolism and hormone secretion. Dopamine lipolys are known to contain two sub-families, D1 and D2, where class D1 bodies (DRD1 and DRD5) regulate the central nervous system reward and movement by activating Gs/Golf and stimulating the production of cyclophosphate adenosine (cAMP). and cognition, and plays a beneficial role in suppressing inflammatory responses and maintaining cardiovascular and kidney dynamic balance in exome tissues, and D2-type subjects (including DRD2, DRD3, and DRD4) are coupled with Gi/Go to inhibit the accumulation of cAMP and regulate different physiological effects.Although important progress has been made in the development of drugs for these five subtypes, the mechanisms for the identification, ligation selectivity, subject activation and G protein selectivity between the five dopamine-like subtypes above
have high sequence ogenosity and the identification of the same endogenesome ligation. So far, the molecular mechanism of D2 receptor identification antagonist formulator and the molecular mechanism of selective astration Bromocriptine activating the DRD2-Gi signal transducting complex have been revealed. However, the structural basis of the D1 sub-family identification distribution is still lacking to provide a theoretical basis for the development of selective astrations, thus unable to meet the clinical needs of drug treatment of Parkinson's disease and high blood pressure with kidney injury, such as high selective astrists.
using cryoelectric technology, the team analyzed for the first time the DRD1-Gs complex in combination with the hypothesol-like astigados (the blood pressure-lowering drug Fenoldopam, the complete agitant A77636 and the G-protein biased astigid SKF83959), the non-cerial teaphenol-like astigist PW0464, and the near-atomic three-dimensional structure combined with dopamine and positive structure regulator LY3154207.
the study has a wide range of effects on dopamine receptor lien recognition, activation process and signal transductivity selection. Its main findings include: revealing the mechanism of the positive binding pocket of DRD1 to identify the endogenous hormone dopamine and cerpedrinophenolic astrogen compound;Using single-particle cryoscopic technology to analyze the complex structure of the dopamine-like DRD1 and G proteins, the
team explained in detail at the atomic level the mechanisms of DRD1's mating recognition, structural regulation, and association with G proteins, and the study will bring new light to drug development and treatment for diseases such as hypertension, Parkinson's syndrome, and kidney injury.
the work related to the frozen electroscope in the research results was completed by Xi'an Technology University. (Source: Wen Caifei, China Science Journal)
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