Unlike Natural Killer (NK) p30, Natural Cytotoxicity Receptor NKp44 Binds to Multimeric α2,3-NeuNAc-Containing N-Glycans

Autor:	Yutaro Azuma, Kojiro Matsumoto, Koji Higai, Mizuha Sakurai, Chihiro Shinoda, Kenichiro Ito, Kazuyuki Yanai
Rok vydání:	2012
Předmět:	Pharmacology chemistry.chemical_classification Glycan biology Mutagenesis Mutant Pharmaceutical Science General Medicine law.invention carbohydrates (lipids) chemistry.chemical_compound Sulfation Sialyl-Lewis X Biochemistry chemistry Transferrin law Recombinant DNA biology.protein Binding site
Zdroj:	Biological and Pharmaceutical Bulletin. 35:594-600
ISSN:	1347-5215 0918-6158
DOI:	10.1248/bpb.35.594
Popis:	Natural cytotoxicity receptor 2 (NCR2 or natural killer (NK)p44) and NCR3 (NKp30) bind to heparin and heparin sulfate; however, other natural ligands have yet to be identified. We previously reported that NCR1 (NKp46) can bind to multimeric NeuNAc-containing N-glycans and sulfated glycans. In this study, we investigated whether NKp44 and NKp30 can bind to NeuNAc-containing glycans using their common recombinant extracellular domain tagged with 6×His (NKp44-H6 and NKp30-H6). NKp44-H6, but not NKp30-H6, bound multimeric sialyl Lewis X expressing transferrin secreted by HepG2 cells (HepTF) with a Kd of 420 nM. Competitive and direct binding assays revealed that NKp44-H6 mainly recognizes α2,3-NeuNAc residues on non-reducing ends of N-glycans on HepTF. Moreover, site-directed mutants of NKp44-H6, such as R47Q, R55Q, R92Q, R95Q, K103Q, and R106Q, had reduced binding to α2,3-sialylated N-glycans. These results suggest that NKp44 binds to α2,3-sialylated N-glycans through ionic interactions, and that these binding sites might have some overlap with heparin binding sites.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::75d7c752b23724f233412ef87178bc7e https://doi.org/10.1248/bpb.35.594 Zobrazit plný text záznamu