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Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody.

Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody.

Authors :
Ishchenko A
Wacker D
Kapoor M
Zhang A
Han GW
Basu S
Patel N
Messerschmidt M
Weierstall U
Liu W
Katritch V
Roth BL
Stevens RC
Cherezov V
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Aug 01; Vol. 114 (31), pp. 8223-8228. Date of Electronic Publication: 2017 Jul 17.
Publication Year :
2017

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-hydroxytryptamine 2B (5-HT <subscript>2B</subscript> ) 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 <subscript>2B</subscript> 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.<br />Competing Interests: The authors declare no conflict of interest.

Details

Language :
English
ISSN :
1091-6490
Volume :
114
Issue :
31
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
28716900
Full Text :
https://doi.org/10.1073/pnas.1700891114