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Glycan Sequence‐Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library
Author(s) -
Wang Ning,
Huang Chengyuan,
Hasegawa Mizuho,
Inohara Naohiro,
Fujimoto Yukari,
Fukase Koichi
Publication year - 2013
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200655
Subject(s) - peptidoglycan , glycan , nod2 , muramyl dipeptide , biochemistry , chemistry , peptide sequence , peptide , muramidase , n acetylglucosamine , enzyme , biology , innate immune system , receptor , in vitro , glycoprotein , gene
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.