Figure 5
Modification of CC′ loop might lead to increase in binding affinity: Panel a illustrates the difference in the CC′ loops of TIGIT (ribbon, green), Nectin-2 (ribbon, yellow) and PVR (ribbon, magenta) when bound to TIGIT (cartoon, light grey). Since, all the three ligands have the same mode of interaction, TIGIT:Nectin-2 and TIGIT:PVR complexes were superposed on TIGIT(surface, green):TIGIT homodimer. Panel b, c and d illustrates the mode of interaction from experimentally determined structures of TIGIT (cartoon, green):TIGIT (cartoon, light grey), Nectin-2 (cartoon, yellow):TIGIT (cartoon, light grey) and PVR (cartoon, magenta):TIGIT (cartoon, light grey). The CC′ loops of the respective structures are shown in sticks. H-bond interactions of CC′ loop of PVR with TIGIT is indicated with black dotted line. Panel e and f depicts the best docked poses of TN:WT-T and TP:WT-T respectively where, modified TIGIT in both e and f panel is represented in green, cartoon and the spliced CC′ loops of Nectin-2 and PVR are represented in sticks, yellow and magenta respectively. Wild type TIGIT in both panels e and f is represented in light grey, cartoon. The interacting residues of TP and TIGIT in panel F are represented in sticks.
