Glycan Sequence-Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library

Ning Wang, Cheng Yuan Huang, Mizuho Hasegawa, Naohiro Inohara, Yukari Fujimoto, Koichi Fukase

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nucleotide oligomerization domain-containing protein 2 (Nod2), an innate immune receptor, recognizes bacterial cell-wall peptidoglycan (PGN), the minimum ligand of which is muramyl dipeptide (MDP). Enzymatic digestion of PGN appears to be important for Nod2 recognition. PGN is degraded by muramidase or glucosamidase through a process that produces two types of glycan sequence; glycans containing GlcNAcβ(1→4)MurNAc or MurNAcβ(1→4)GlcNAc. In this report, a range of disaccharide or tetrasaccharide fragments of each sequence were chemically synthesized, and their activities in stimulating human Nod2 (hNod2) were investigated. The results reveal that hNod2 recognitions is dependent on the glycan sequence, as demonstrated by comparing the activities of glycans with the same peptide moieties. (MurNAcβ(1→4)GlcNAc)2-containing structures exhibited stronger activity than those containing (GlcNAcβ(1→4)MurNAc)2. The results suggest that differences in the enzymatic degradation process affect the host's immunomodulation process.

Original languageEnglish
Pages (from-to)482-488
Number of pages7
JournalChemBioChem
Volume14
Issue number4
DOIs
Publication statusPublished - 2013 Mar
Externally publishedYes

Fingerprint

Nod2 Signaling Adaptor Protein
Oligomerization
Peptidoglycan
Polysaccharides
Nucleotides
Chemical activation
Proteins
Acetylmuramyl-Alanyl-Isoglutamine
Immunomodulation
Disaccharides
Muramidase
Cell Wall
Digestion
Ligands
Degradation
Peptides

Keywords

  • Compound libraries
  • Glycosylation
  • Nod2
  • Peptidoglycans

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Glycan Sequence-Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library. / Wang, Ning; Huang, Cheng Yuan; Hasegawa, Mizuho; Inohara, Naohiro; Fujimoto, Yukari; Fukase, Koichi.

In: ChemBioChem, Vol. 14, No. 4, 03.2013, p. 482-488.

Research output: Contribution to journalArticle

Wang, Ning ; Huang, Cheng Yuan ; Hasegawa, Mizuho ; Inohara, Naohiro ; Fujimoto, Yukari ; Fukase, Koichi. / Glycan Sequence-Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library. In: ChemBioChem. 2013 ; Vol. 14, No. 4. pp. 482-488.
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