Peptidoglycan Molecular Requirements Allowing Detection by Nod1 and Nod2*

By S. Girardin, L. Travassos, M. Hervé, D. Blanot, I. Boneca, D. Philpott, P. Sansonetti, D. Mengin-Lecreulx. Journal of Biological Chemistry, 2003

676 citations recorded by the source corpus.

Nod1 and Nod2 are mammalian proteins implicated in the intracellular detection of pathogen-associated molecular patterns. Recently, naturally occurring peptidoglycan (PG) fragments were identified as the microbial motifs sensed by Nod1 and Nod2. Whereas Nod2 detects GlcNAc-MurNAc dipeptide (GM-Di), Nod1 senses a unique diaminopimelate-containing GlcNAc-MurNAc tripeptide muropeptide (GM-TriDAP) found mostly in Gram-negative bacterial PGs. Because Nod1 and Nod2 detect similar yet distinct muropeptides, we further analyzed the molecular sensing specificity of Nod1 and Nod2 toward PG fragments. Using a wide array of natural or modified muramyl peptides, we show here that Nod1 and Nod2 have evolved divergent strategies to achieve PG sensing. By defining the PG structural requirements for Nod1 and Nod2 sensing, this study reveals how PG processing and modifications, either by host or bacterial enzymes, may affect innate immune responses.

Subfields: Epidemiology, Microbiology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/3c92ea1676210f33b3a9da9b72fa80bdd47c096f

How researchers see this paper

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In Epidemiology

1. G. Núñez
2. B. B. Finlay
3. B. Beutler
4. G. McFadden
5. Judy H. Cho

In Microbiology

1. B. B. Finlay
2. B. Beutler
3. G. McFadden
4. R. Ferrero

In Public Health, Environmental and Occupational Health

1. G. Núñez
2. Judy H. Cho
3. R. Ferrero

Citations in the corpus

• The genetics and immunopathogenesis of inflammatory bowel disease (2008, background): “NOD2 is a pattern-recognition receptor that functions as an intracellular sensor for bacterial peptidoglycan and that can be activated by a minimal bioactive component of peptidoglycan, muramyl dipeptide (MDP”
• Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. (2006, background): “Human Nod1 detects N-acetylglucosamine-N-acetylmuramic acid, a tripeptide motif characteristic of Gram negative organisms (Girardin et al., 2003a), while Nod2 detects a N-acetylglucosamine- N-acetylmuramic acid dipeptide (Girardin et al., 2003b).”
• Innate immunity: an overview. (2004, background): “In addition, intracellular proteins with motif similarity (though not primary structural homology) to defensive proteins of plants have been suggested to serve a role as intracytoplasmic microbial sensors (Girardin et al., 2003a,b; Girardin et al., 2003 ).”
• Function of Nod‐like receptors in microbial recognition and host defense (2009, background): “DAP is an usual amino acid residue that is unique to PGN from most Gram-negative bacteria and certain Gram-positive bacteria, including the genus Listeria and Bacillus species (39).”
• Cytoplasmic steps of peptidoglycan biosynthesis. (2008, methodology): “…has been exploited for the synthesis of nucleotides containing unusual amino acids at position 3, such as LL-A2pm (Mengin-Lecreulx et al., 1988), mesolanthionine and L-allo-cystathionine (Mengin-Lecreulx et al., 1994), L-ornithine, L-aminopimelate and amidated meso-A2pm (Girardin et al., 2003).”
• Nod-like proteins in immunity, inflammation and disease (2006, background): “The optimal peptidoglycan motifs detected by human and mouse Nod1 are structures containing L -Ala-γ- D -Glu- meso -DAP and L -Ala-D-glu- meso DAP- D -Ala, respectively, and the minimal activating structure is the dipeptide γ- D -Glu- meso -DA”