FIGURE 8.

A schematic of the two-site multistep binding of CXCL8 to its receptor. The structural scaffold of CXCL8 is shown in black, the 30s loop in pink, disulfides in blue, and the N-terminal residues are in black (panel A). The figures are not to scale and are purely for illustrative purposes only. The initial binding interactions at Site-I results in structural/dynamic changes that are essential for subsequent binding of N-terminal ELR residues to receptor transmembrane/extracellular loop residues and receptor activation (Site-II, panel B). The absence of the spacer X (CXC to CC) nevertheless allows binding and activation at Site-II for CXCR1 (panel C) but not CXCR2 (panel D).