Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT 1F –G protein complex
Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT 1F –G protein complex
Abstract Migraine headache has become global pandemics and is the number one reason of work day loss. The most common drugs for anti-migraine are the triptan class of drugs that are agonists for serotonin receptors 5-HT1B and 5-HT1D. However, these drugs have side effects related to vasoconstriction that could have fatal consequences of ischemic heart disease and myocardial infarction. Lasmiditan is a new generation of anti-migraine drug that selectively binds to the serotonin receptor 5-HT1F due to its advantage over the tripan class of anti-migraine drugs. Here we report the cryo-EM structure of the 5-HT1F in complex with Lasmiditan and the inhibitory G protein heterotrimer. The structure reveals the mechanism of 5-HT1F-selective activation by Lasmiditan and provides a template for rational design of anti-migraine drugs.
Xu Peiyu、Tan Yangxia、You Chongzhao、Jiang Yi、Xu H. Eric、Zhang Yumu、Huang Sijie
The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of SciencesThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of Sciences||School of Life Science and Technology, ShanghaiTech UniversityThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of SciencesThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of SciencesThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of Sciences||School of Life Science and Technology, ShanghaiTech UniversityThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of Sciences||School of Life Science and Technology, ShanghaiTech UniversityThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences||University of Chinese Academy of Sciences||School of Life Science and Technology, ShanghaiTech University
药学基础医学神经病学、精神病学
Xu Peiyu,Tan Yangxia,You Chongzhao,Jiang Yi,Xu H. Eric,Zhang Yumu,Huang Sijie.Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT 1F –G protein complex[EB/OL].(2025-03-28)[2025-06-23].https://www.biorxiv.org/content/10.1101/2021.05.29.446083.点此复制
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