Nod1

NOD-1 ("Nucleotide-binding oligomerization domain-containing protein 1"), also known as NLRC1, is a protein receptor that in humans is encoded by the NOD1 gene (chromosomal locus 7p14.3). NOD1 is a cytoplasmic recognition receptor (PPR) that is comparable in structure to plant PPRs.

NOD-like receptors (NLRs) are cytoplasmic (non-membrane) protein receptors that recognize mainly bacterial lipopolysaccharides and peptidoglycans. Like Toll-like receptors, NOD-like receptors belong to the large group of pathogen recognition receptors (PPR). NOD-like receptors represent an important component of innate immunity.

Biochemically, NOD-like receptors (NLR) are characterized by a three-part domain structure:

Centrally located is the eponymous NOD domain (nucleotide binding oligomerization domain - NOD), C-terminally located are leucine-rich repeats (LRR). N-terminally, the effector domains CARD, pyrin or BIR are bound. PAMPs (also MAMPs-microbial/pathogen associated molecular pattern) are recognized and bound via the leucine-rich docking sites. The N-terminal domain defines which signaling pathways are induced downstream upon receptor activation.

NOD-like receptors activate an inflammatory response via the expression of antimicrobial peptides. Furthermore, NOD-like receptors induce processes of apoptosis via mechanisms that have not yet been clearly elucidated.

In principle, NLRs can be divided into 2 main groups with respect to their functionality: the NLRC group with the two main representatives NOD1 and NOD2, and the inflammasome-activating NLRs with their main representatives, the NLRPs.

NOD1, together with other PPRs, organizes natural and acquired immunity by recognizing bacterial components of microbial (highly conserved) polypeptide glycans, which are the basic scaffold of the bacterial cell wall. These are also known as microbial-associated molecular patterns - MAMPs. NOD1 receptors thus represent the 2nd instance in the recognition of bacteria.

Versch. Polymorphisms of the NOD1 and NOD2 genes are associated with an increased risk of developing gastric cancer. Probably the increased carcinoma risk is caused by an increased colonisation by Helicobacter pylori, due to the disturbed immune defence. This observation also underlines the importance of intact NOD receptors in the defence against bacterial infections (Zhou YJ et al. 2015)

A similar finding can be made for NOD1 polymorphisms also for Chlamydia trachomatis infections (Branković I et al. 2015).

However, recent studies suggest that NOD1 activation can occur not only through bacterial antigens but also through viral antigens, as demonstrated by the example of hepatitis C virus infections (Vegna S et al. 2016).

In patients with metabolic syndrome an increased expression of NOD1 but not NOD2 in the fat depots is detectable. Elevated NOD1 levels correlated positively with elevated HBA-1c levels and with elevated serum levels of interleukin-6 and NF-κB.

1. Branković I et al (2015) NOD1 in contrast to NOD2 functional polymorphism influence Chlamydia trachomatis infection and the risk of tubal factor infertility. Pathog Dis 73:1-9.
2. Kaparakis-Liaskos M (2015) The intracellular location, mechanisms and outcomes of NOD1 signaling. Cytokines 74:207-212.
3. Vegna S et al (2016) NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase. J Virol 90:6022-6035.
4. Zhou YJ et al (2015) Increased NOD1, but not NOD2, activity in subcutaneous adipose tissue from patients with metabolic syndrome. Obesity (Silver Spring) 23:1394-1400.