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Dual specificity of Langerin to sulfated and mannosylated glycans via a single C-type carbohydrate recognition domain.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2010 Feb 26; Vol. 285 (9), pp. 6390-400. Date of Electronic Publication: 2009 Dec 21. - Publication Year :
- 2010
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Abstract
- Langerin is categorized as a C-type lectin selectively expressed in Langerhans cells, playing roles in the first line of defense against pathogens and in Birbeck granule formation. Although these functions are thought to be exerted through glycan-binding activity of the C-type carbohydrate recognition domain, sugar-binding properties of Langerin have not been fully elucidated in relation to its biological functions. Here, we investigated the glycan-binding specificity of Langerin using comprehensive glycoconjugate microarray, quantitative frontal affinity chromatography, and conventional cell biological analyses. Langerin showed outstanding affinity to galactose-6-sulfated oligosaccharides, including keratan sulfate, while it preserved binding activity to mannose, as a common feature of the C-type lectins with an EPN motif. By a mutagenesis study, Lys-299 and Lys-313 were found to form extended binding sites for sulfated glycans. Consistent with the former observation, the sulfated Langerin ligands were found to be expressed in brain and spleen, where the transcript of keratan sulfate 6-O-sulfotransferase is expressed. Moreover, such sulfated ligands were up-regulated in glioblastoma relative to normal brain tissues, and Langerin-expressing cells were localized in malignant brain tissues. Langerin also recognized pathogenic fungi, such as Candida and Malassezia, expressing heavily mannosylated glycans. These observations provide strong evidence that Langerin mediates diverse functions on Langerhans cells through dual recognition of sulfated as well as mannosylated glycans by its uniquely evolved C-type carbohydrate-recognition domain.
- Subjects :
- Animals
Brain Neoplasms chemistry
CHO Cells
Cricetinae
Cricetulus
Fungi metabolism
Glioblastoma chemistry
Humans
Langerhans Cells
Ligands
Protein Array Analysis
Protein Binding
Antigens, CD metabolism
Lectins, C-Type metabolism
Mannose
Mannose-Binding Lectins metabolism
Polysaccharides metabolism
Sulfates
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 285
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20026605
- Full Text :
- https://doi.org/10.1074/jbc.M109.041863