The conservative polarity pocket is a common activation mechanism for type B GPCR.

The type B secretion GPCR family consists of 15 peptide hormones, including glutatrogen, vascular active enteropeptides, glutatrogen-like peptides and thyroid hormones, etc., which play a key role in hormone balance regulation in the body and are important drug targets for treating bone diseases, metabolic diseases and neurological diseases.
drug development based on its downstream signaling path is difficult because little is known about the activation mechanism and configuration changes of the family receptor.
Xu Huaqiang of the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences, in collaboration with Wang Mingwei, recently discovered a new activation mechanism for the G protein-coupled receptor (G protein-coupled receptor, GPCR).
March 30, the International Journal of Biochemistry published a research paper online entitled Realrangement of a polar core provides a conserved mechanism for constitutive of class activation B G protein-coupled receptors. the conservative amino acids of
B GPCR TM2, TM3, TM6 and TM7 stabilize the inactive configuration of the receptor by forming polar pockets The study took the glutamate receptor as the research object, and proposed the molecular mechanism of its activation, that is, the receptor sixth transmeanor region is restricted to the inactive polarity pocket and hydrophobic region, and destroying these two key domains will cause the structure of the sixth transduction zone to change the self-activation effect.
researchers also found that the recombination of the conservative polarity pocket also led to the self-activation of other type B GPCR (e.g. vascular active intestinal peptide i, adrenal corticosteroid release factor I, thyroid hormone inhibitor I and pituitary glandular glandularase activation polypeptides I, etc.), indicating that recombinant the conservative polar pocket is a common activation mechanism of B-type GPCR.
the study also explains what was observed 20 years ago, namely, why double-bit mutations in thyroid hormones in the thyroid hormone complex cause the subject to self-activate, leading to Jansen's Metaphyseal Chondrodysplasia, a congenital cartilage development disorder.
the first author of this paper is Yin Yanxuan, Ph.D., Xu Huaqiang Of Shanghai Pharmaceutical Institute, and the correspondent is Xu Huaqiang and Wang Mingwei, researchers selected for the National "Thousand People Program".
The research work was carried out by Shanghai Pharmaceutical Institute, Wen'an Lo Research Institute of the United States, Fudan University and other institutions, and received strong support from the National Natural Science Foundation of China, Wen'anlo Fund Project, NIH Fund Project, Ministry of Science and Technology Project, Chinese Academy of Sciences Strategic Pilot Science and Technology Special (Category B), Shanghai Science and Technology Development Fund, CASNO and NORD Research Fund.
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