Table 3. DNA ligand structures that indicate non-self.
Structure | Recognized structure | Receptor or effector molecule | Origin |
---|---|---|---|
|
Base-paired DNA ≥40-80 bp (≥25 bp in mouse cells) | cGAS, AIM2 (human); cGAS (mouse) | Eukaryotic genomic DNA, bacterial plasmid DNA, dsDNA viruses and lentivirus dsDNA |
|
G-rich Y-form DNA: base paired DNA ≥12 bp plus unpaired G in adjacent ssDNA (G indicated in red) | cGAS | Long ssDNA with secondary structures: reverse transcripts (cDNA) of lentiviruses, endogenous retroviruses and retroelements |
...CG.. | CpG-rich DNA. CpG methylation blocks TLR9 recognition | TLR9 | Unmethylated DNA from bacteria; DNA from viruses and host |
...ATATATATATATATATATATATATATATATA.. | AT-rich 'ssDNA'* | RNA polymerase III and RIG-I | Unclear |
|
Long DNA–RNA hybrids | cGAS | Reverse transcript of cDNA–RNA template hybrids of lentiviruses, endogenous retroviruses and retroelements |
|
Short DNA–RNA hybrid | TLR9 | Hybrids of RNA transcripts plus DNA template (RNase H deficiency) |
AIM2, absent in melanoma 2; cGAS, cyclic GMP–AMP synthetase; dsDNA, double-stranded DNA; ssDNA, single-stranded DNA; RIG-I, retinoic acid inducible gene I; RNase H, ribonuclease H; TLR9, Toll-like receptor 9.
*A self-complementary ssDNA that in principle is only unpaired at high temperature.