Based on a structural comparison of the surface charges in the TLR3 and TLR9 N-termini (red = negatively, blue = positively charged), mutations were introduced in TLR9. Whereas histidines conserved in sequence did not alter responsiveness to the CpG ligand, mutations of structurally equivalent K51 and R74 abrogated responsiveness (right) and ligand binding (not shown). This illustrates the advantages of structural approachs to determine ligand-receptor interaction principles. Read more: Peter et al. Journal of Immunology 2009