Figure 4. Biased agonists induced conformational changes in the CR and the lower half of TM7.

(A) In the CR, biased agonist binding (blue) splits the side chains of W293^6.48 and A117^2.53, which allows TM7 to approach TM3. The movements are measured by (B) the minimum side-chain distances between W293^6.48 and A117^2.53, against the Cα distances between I155^3.40 and N328^7.45. (C) Schematic presentation of the inter-helical movements. Arrows indicate the direction of the movements and dashed lines indicates the distances measured for (B and E). (D) In the lower half of TM7, the N^7.49P^7.50xxY^7.53 motif moves away from the G^1.49N^1.50 motif in TM1 only for biased agonists. This is measured by (E) the side-chain distances between N86^1.50, N332^7.49 and Y336^7.53.