Figure 9

Illustrating the “two-site” binding paradigm of hC5a to C5aR. Step1: Wrapping of NT of C5aR (site1) around the allosteric region of hC5a with high affinity, triggering local conformational change both at the ECS of C5aR and at the CT of hC5a. Step2: Docking of the conformationally altered CT of hC5a at the ECS (site2) of C5aR triggering global conformational change in the overall complex, and further opening of the intracellular face of C5aR for downstream signaling.