Fig. 1: Nanobody selection and cryo-EM structure of CB1R inactive state.
From: Structural mechanism of CB1R binding to peripheral and biased inverse agonists
A Schematic of nanobody selection process. Yeast displaying nanobodies were incubated with purified CB1R-PGS. Specific binders were enriched using iterative rounds of MACS and FACS selection. B Cryo-EM structure of taranabant bound CB1R-CNb36 complex. CB1R is depicted in gray, PGS in blue, and CNb36 in green, with an inset emphasizing the CDRs of the nanobody. CDR1 is illustrated in green, CDR2 is pink, and CDR3 is yellow. C Zoomed-in view of the CDRs contacting CB1R (gray surface) and PGS (blue surface). D View of the interaction between the CDRs and CB1R-PGS colored according to electrostatic surface potential. E Superposition of the crystal structure of CB1R-PGS with taranabant (PDB: 5U09) and the cryo-EM structure of CB1R-PGS bound to taranabant (PDB: 9B9Y), using the receptor Cα positions. The overlay show high similarity of the receptors, despite a 64° rotation of the PGS domain (blue in the cryo-EM structure, cyan in the crystal structure). Taranabant binding (right) is almost identical between the cryo-EM structure (yellow sticks) and the crystal structure (brown sticks).
