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

• Published in: Chembiochem : a European journal of chemical biology Vol. 14; no. 4; pp. 482 - 488
• Main Authors: Wang, Ning, Huang, Cheng-yuan, Hasegawa, Mizuho, Inohara, Naohiro, Fujimoto, Yukari, Fukase, Koichi
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.03.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Bacteria; Beta; Biochemistry & Molecular Biology; Carbohydrate Sequence; Chemistry, Medicinal; compound libraries; glycosylation; Gram-Positive Bacteria - chemistry; Gram-Positive Bacteria - immunology; HEK293 Cells; Humans; Life Sciences & Biomedicine; Microbiology; Molecular Sequence Data; Nod2; Nod2 Signaling Adaptor Protein - immunology; Peptidoglycan - chemistry; Peptidoglycan - immunology; peptidoglycans; Pharmacology & Pharmacy; Science & Technology; CROHNS-DISEASE; HOST RECOGNITION; compound libraries; SUSCEPTIBILITY; GLYCOSYL; glycosylation; peptidoglycans; Nod2; DIAMINOPIMELIC ACID
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201200655

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. To Nod off or on? Di‐ or tetrasaccharide fragments of muramidase and glucosamidase were chemically synthesized, and their abilities to stimulate human Nod2 were investigated. The results reveal that hNod2 recognition is glycan sequence‐dependent, and suggest that the peptidoglycan degradation process affects the host's immunomodulation.