Nod-like receptors

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

NLR; NOD-like-receptor; Nucleotide-binding Oligomerization Domain

Definition
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NOD-like receptors (NLR) are cytoplasmic proteins that recognize bacterial lipopolysaccharides and peptidoglycans. Like toll-like receptors, they belong to the large group of pathogen recognition receptors (PPR). NOD-like receptors are an important component of innate immunity.

Classification
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In contrast to other PRRs such as Toll-like receptors, NOD-like receptors (NLRs) are not transmembrane proteins but soluble, cytoplasmic proteins. They are mainly expressed in lymphocytes and antigen-presenting cells, but also in epithelial cells.

The 22 NLRs currently known in humans are divided into 5 groups (NLRA, NLRB, NLRC, NLRP, NLRX) (Inohara N et al. 2003):

  1. NLRA (acidic transactivation domain, AD) -CITA
  2. NLRB (baculovirus inhibitor of apoptosis protein repeat - BIR). The NLRB group was formerly known as NAIP or Birc
  3. NLRC (Caspase activation and recruitment domain, CARD), with the two main representatives NOD1 and NOD2 as well as the NOD-like receptors NLRP3 (NLPR3 is also called "cryopyrin"), NLRP4, NLRP5. NLRC group was formerly called NODs.
  4. NLRP (Pyrin domain, PYD) with the most important representatives: NLRP1, NLRP2-9, NLRP11-14, NLRP10. NLRPs were formerly called NALPs
  5. NLRX (functions and components are still unknown)
  6. The 22 NLRs currently known in humans are divided into 5 subgroups (NLRA, NLRB, NLRC and NLRP) (Inohara N et al. 2003)

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

    Centrally located is the nucleotide binding oligomerization domain (NOD), C-terminal are leucine-rich repeats (LRR). The effector domains CARD, pyrin or BIR are bound N-terminal.

    PAMPs (also MAMPs-microbial/pathogen associated molecular pattern) are recognized and bound via the leucine-rich docking sites. The N-terminal domain defines which signalling pathways are induced downstream when the receptors are activated.

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

    Note(s)
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    In principle, the NLRs can be divided into 2 main groups with regard to their function: the NLRC group with the two main representatives NOD1 and NOD2 and the NLRs activating inflammasome with their main representatives the NLRPs.

    NOD1 and NOD2 recognize components of peptidoglycan, which form the main scaffold of the bacterial cell wall. Thus, after the toll-like receptors, they provide a second cytoplasmic barrier to eliminate bacteria that have escaped recognition of cell membrane-bound receptors.

    NLRPs activate the inflammasome, a multi-protein complex. Activation of the inflammasome leads to expression of caspases that convert inactive interleukin-1beta and interleukin-18 into their biologically active form. NLRP3 is also called cryopyrin.

    The physiological significance of NLR is shown by disease patterns that are due to genetic mutations (autoinflammatory diseases), and which are characterized by chronic inflammatory or autoimmunological processes.

    Literature
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    1. Franchi L et al (2008) Intracellular NOD-like receptors in innate immunity, infection and disease.Cell Microbiol 10:1-8.

    2. Inohara N et al (2003) Nods: Intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 3: 371-382

    3. Martinon F (2008). Detection of immune danger signals by NALP3. J Leukoc Biol 83: 507-11

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    Last updated on: 29.10.2020