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-HT2B) 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-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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 Vdoi
10.1073/pnas.1700891114subject
Has Abstractpub_date
2017-08-01 00:00:00pages
8223-8228issue
31eissn
0027-8424issn
1091-6490pii
1700891114journal_volume
114pub_type
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