According to our latest data (Peter et al. Journal of Immunology 2009 and Kubarenko et al. under review) TLR9 binds CpG-DNA at two distinct sites (red). Additional regions, for example N-terminal leucine-rich repeat insertions, contribute to sensing the ligand. The distance between site 1 and 2 can be spanned by a 16 bp oligonucleotide and it is conceivable that different relative positions exist between two TLR9 monomers engaging the same DNA molecule simultaneously. Read more