Figure 6.

Impact of the chemokine X-factor. A, the two determined co-crystal structures of CC and CXC receptors display unique chemokine binding orientations. The CC chemokine body interacts closely with the receptor core and includes penetration of the 30s loop into the orthosteric pocket. The CXCR4 co-crystal complex has vMIP-II above the extracellular vestibule with few interactions between the receptor and the 30s loop. B, a proposed model describing the potential influence of the X-factor between CC and CXC chemokines. The X residue directly interacts with the β1-β2 hairpin to stabilize this region in an extended conformation. The loss of the X position pulls the 30s loop into a narrow conformation that favors the increased CC binding depth. Additionally, the presence of the X position constrains the orientation of the chemokine N terminus in solution. The more linear N terminus found in CXC structures matches with the chemokine position above the receptor pocket in the co-crystal structure.