5TUD

Structural Insights into the Extracellular Recognition of the Human Serotonin 2B Receptor by an Antibody

Summary for 5TUD

• Entry DOI: 10.2210/pdb5tud/pdb
• Related: 4NC3
• Descriptor: 5-hydroxytryptamine receptor 2B,Soluble cytochrome b562 chimera, Anti-5-HT2B Fab light chain, Anti-5-HT2B Fab heavy chain, ... (4 entities in total)
• Functional Keywords: 7-tm, gpcr, fab, complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 201427.99

Authors

Ishchenko, A.,Wacker, D.,Kapoor, M.,Zhang, A.,Han, G.W.,Basu, S.,Boutet, S.,James, D.,Wang, D.,Weierstall, U.,Liu, W.,Katritch, V.,Stevens, R.C.,Cherezov, V. (deposition date: 2016-11-05, release date: 2017-07-26, Last modification date: 2024-10-30)

Primary citation

Ishchenko, A.,Wacker, D.,Kapoor, M.,Zhang, A.,Han, G.W.,Basu, S.,Patel, N.,Messerschmidt, M.,Weierstall, U.,Liu, W.,Katritch, V.,Roth, B.L.,Stevens, R.C.,Cherezov, V.
Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody.
Proc. Natl. Acad. Sci. U.S.A., 114:8223-8228, 2017

PubMed 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) 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 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.

PubMed: 28716900
DOI: 10.1073/pnas.1700891114

Experimental method

X-RAY DIFFRACTION (3 Å)