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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.
- 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.
- Subjects :
- Antibodies, Monoclonal chemistry
Antibodies, Monoclonal metabolism
Binding, Competitive
Catalytic Domain
Crystallography, X-Ray
Epitopes chemistry
Epitopes metabolism
Ergotamine chemistry
Ergotamine metabolism
Humans
Immunoglobulin Fab Fragments metabolism
Models, Molecular
Protein Conformation
Receptor, Serotonin, 5-HT2B metabolism
Serotonin Receptor Agonists chemistry
Serotonin Receptor Agonists metabolism
Immunoglobulin Fab Fragments chemistry
Receptor, Serotonin, 5-HT2B chemistry
Receptor, Serotonin, 5-HT2B immunology
Subjects
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