2n7b | pdb_00002n7b

Solution structure of the human Siglec-8 lectin domain in complex with 6'sulfo sialyl Lewisx

spinqualitylabelsall models 2n7b, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2n7b is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0D8, FUC, G6S, NAG, SIA Related: 2n7a Gene: SIGLEC8, SAF2 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SIGL8_HUMAN] Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3-linked sialic acid. Also binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. Publication Abstract from PubMed Siglec-8 is a human immune-inhibitory receptor that, when engaged by specific self-glycans, triggers eosinophil apoptosis and inhibits mast cell degranulation, providing an endogenous mechanism to down-regulate immune responses of these central inflammatory effector cells. Here we used solution NMR spectroscopy to dissect the fine specificity of Siglec-8 toward different sialylated and sulfated carbohydrate ligands and determined the structure of the Siglec-8 lectin domain in complex with its prime glycan target 6'-sulfo sialyl Lewis(x) A canonical motif for sialic acid recognition, extended by a secondary motif formed by unique loop regions, recognizing 6-O-sulfated galactose dictates tight specificity distinct from other Siglec family members and any other endogenous glycan recognition receptors. Structure-guided mutagenesis revealed key contacts of both interfaces to be equally essential for binding. Our work provides critical structural and mechanistic insights into how Siglec-8 selectively recognizes its glycan target, rationalizes the functional impact of site-specific glycan sulfation in modulating this lectin-glycan interaction, and will enable the rational design of Siglec-8-targeted agonists to treat eosinophil- and mast cell-related allergic and inflammatory diseases, such as asthma. Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8.,Propster JM, Yang F, Rabbani S, Ernst B, Allain FH, Schubert M Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4170-9. doi:, 10.1073/pnas.1602214113. Epub 2016 Jun 29. PMID:27357658 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Core-binding factor

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