2N7A
Solution structure of the human Siglec-8 lectin domain
Summary for 2N7A
| Entry DOI | 10.2210/pdb2n7a/pdb |
| Related | 2N7B |
| NMR Information | BMRB: 25798 |
| Descriptor | Sialic acid-binding Ig-like lectin 8 (1 entity in total) |
| Functional Keywords | sialic acid-binding immunoglobulin-like lectin 8, siglec8, saf-2, i-type lectin, carbohydrate-binding receptor, structural protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: Q9NYZ4 |
| Total number of polymer chains | 1 |
| Total formula weight | 16665.46 |
| Authors | Proepster, J.M.,Yang, F.,Rabbani, S.,Ernst, B.,Allain, F.H.-T.,Schubert, M. (deposition date: 2015-09-07, release date: 2016-07-06, Last modification date: 2024-11-20) |
| Primary citation | Propster, J.M.,Yang, F.,Rabbani, S.,Ernst, B.,Allain, F.H.,Schubert, M. Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8. Proc.Natl.Acad.Sci.USA, 113:E4170-E4179, 2016 Cited by PubMed Abstract: 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. PubMed: 27357658DOI: 10.1073/pnas.1602214113 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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