NOD and Toll Like Receptor Protein

NOD proteins

Cytosolic and has two members in this family i.e. NOD1 and NOD2, which recognize products derived from bacterial peptidoglycans.

NOD1 binds to the tripeptide products of peptidoglycans (NAM and NAG) breakdown and NOD2 recognizes muramyl dipeptide, derived from the degradation of peptidoglycan from gram positive bacterial cell walls.

NOD1 recognizes meso-diaminopimellic acid (meso-DAP) in Gram –ve bacteria and NOD2 senses intracellular muramyl dipeptide (MDP) in S. Pneumoniae and M.tuberculosis.

Mutation of NOD2 is associated with crohn’s disease or Blau syndrome. 

Toll Like Receptor proteins (TLR)

Membrane spanning proteins that share a common structural element in their extracellular region, repeating segments of 24 to 29 amino acids containing the sequence xLxxLxLxx. These structural motifs are called leucine rich repeats. The intracellular domain of TLR is called TIR domain.

TLR1 à ligand is Triacyl lipopeptides and a target microbe is mycobacteria.

TLR2 à ligand is peptidoglycans, GPI linked proteins, lipoproteins and zymosan. Target molecules are gram positive bacteria, trypanosomes, mycobacteria, yeasts and other fungi.

TLR3 à double stranded RNA (dsRNA) and target microbes are viruses.

TLR4 àLPS and F-protein and target microbes are Gram –ve and respiratory syncytial virus (RSV)

TLR5 à flagellin and target is bacteria.

TLR6 à diacyl lipopeptides and zymosan. Mycobacteria, yeast and fungi.

TLR7 à single stranded RNA (ssRNA) and viruses.

TLR8 à single stranded RNA (ssRNA) and viruses.

TLR9 à CpG unmethylated dinucleotides, dinucleotides, herpesvirus infection. Bacterial DNA and some herpesvirus

TLR10 and TLR11 à unknown