文章基本信息

标题：Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody
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作者：Andrii Ishchenko ; Daniel Wacker ; Mili Kapoor 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：31
页码：8223-8228
DOI：10.1073/pnas.1700891114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Monoclonal antibodies provide an attractive alternative to small-molecule therapies for a wide range of diseases. Given the importance of G protein-coupled receptors (GPCRs) as pharmaceutical targets, there has been an immense interest in developing therapeutic monoclonal antibodies that act on GPCRs. Here we present the 3.0-Å resolution structure of a complex between the human 5-hydroxytryptamine 2B (5-HT_2B) receptor and an antibody Fab fragment bound to the extracellular side of the receptor, determined by serial femtosecond crystallography with an X-ray free-electron laser. The antibody binds to a 3D epitope of the receptor that includes all three extracellular loops. The 5-HT_2B receptor is captured in a well-defined active-like state, most likely stabilized by the crystal lattice. The structure of the complex sheds light on the mechanism of selectivity in extracellular recognition of GPCRs by monoclonal antibodies.
关键词：GPCR ; active state ; antibody recognition ; X-ray free-electron laser ; serial femtosecond crystallography