- Science Director Dr. John Spence named Royal Society Fellow
- BioXFEL Graduate Student Joey Olmos (Rice) Earns NSF Graduate Research Fellowship
- Mapping Conformational Landscape Through Crystallography
- NSF BioXFEL researchers create a better way to find out ‘when’
- Taking the initiative on single particle imaging
- Thursday, 27 July 2017 11:06
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.