At present, there are more than 1 billion people suffering from migraine "tightening curse" worldwide
Recently, the team of Xu Huaqiang, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, used cryo-electron microscopy to analyze the complex structure of 5-HT1F receptor binding G protein and the anti-migraine drug lamitetan for the first time, revealing the selectivity of lamitetan Bind to the structural basis of 5-HT1F receptor
Migraine is a neurological disease with a very wide range of effects.
Serotonin (5-HT) family receptors are important targets for central nervous system diseases such as migraine, depression, and schizophrenia
Xu Huaqiang said in an interview with "China Science Daily" that serotonin is involved in the regulation of many basic physiological functions such as memory, mood, appetite, and sleep in the human brain
For many years, triptans, which are agonists targeting 5-HT1B/1D, have been widely used in the treatment of migraine
With the approval of lamitetan, 5-HT1F, as a promising anti-migraine target, is of great significance to the study of its structure, function, and mechanism of action of selective drugs
5-HT1F is a member of the 5-HT1 subfamily, but it is relatively different from other subtypes of this subfamily in terms of homology and ligand activation effects, which also makes 5-HT1F a potential selective anti-migraine Target
"In order to obtain a high-quality complex structure, it is necessary to go through a series of complex purification processes to obtain a sufficient amount, high purity, and good stability of the sample
Not only that, the low expression level of 5-HT1F receptor-G protein complex and the unstable assembly of the complex also brought many difficulties for the preparation and structural analysis of frozen samples
Through exploration of conditions such as purification, frozen sample preparation, and data processing, Xu Huaqiang's team finally broke through the technical bottleneck of low expression of 5-HT1F receptor-G protein complex and unstable complex assembly, and obtained high-quality complexes.
"At present, the structure of multiple subtypes of the serotonin receptor family has not yet been resolved.
The research was funded by the National Key Research and Development Program, the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences, the Shanghai Municipal Science and Technology Major Project, the National Natural Science Foundation of China, and the National Science and Technology Major Project
Related paper information: https://doi.
https://doi.
org/10.
1038/s41422-021-00527-4
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