1. Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody.
- Author
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Ishchenko, Andrii, Wacker, Daniel, Kapoor, Mili, Ai Zhang, Gye Won Han, Basu, Shibom, Patel, Nilkanth, Messerschmidt, Marc, Weierstall, Uwe, Wei Liuh, Katritche, Vsevolod, Roth, Bryan L., Stevens, Raymond C., and Cherezov, Vadim
- Subjects
SEROTONIN receptors ,MONOCLONAL antibodies ,G protein coupled receptors ,CRYSTALLOGRAPHY ,ERGOTAMINE (Drug) ,ENZYME-linked immunosorbent assay - Abstract
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-hydroxy-tryptamine 2B (5-HT
2B ) receptor and an antibody Fab fragment bound to the extracellular side of the receptor, determined by serial femto-second crystallography with an X-ray free-electron laser. The anti-body binds to a 3D epitope of the receptor that includes all three extracellular loops. The 5-HT2B 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. [ABSTRACT FROM AUTHOR]- Published
- 2017
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