Figure 5. Agonist and loop movements in the hold (flip and flop).

(A) Left, superimposed cartoons of AC_L (m1; orange) and AC_H (m3; blue). Loop C is upper left and loop F is lower right. In L→H (orange→blue) there is a cis→trans reorientation of the agonist (flip) and a downward movement of loop C (flop, arrow). Right, agonist structure m1 (red) versus m2 (yellow) versus m3 (blue). Degree pertains to the m1→m3 pivot angle of the agonist.

Figure 5—figure supplement 1. Conformational change of the pocket cavity accommodates agonist re-orientation.

Red, low-affinity conformation (AC_L); blue, high-affinity conformation (AC_H). In AC_L the ligand is cis and aromatic residues αY190, αY93, and δW57 are spread to accommodate the agonist’s tail. In AC_H the ligand is trans and αY190 is positioned to fill the αY93-δW57 gap, creating a unified surface that restrains the ligand’s tail. Key residue sidechains are shown as spheres; the agonist is ball-and-stick.