2N7A

Solution structure of the human Siglec-8 lectin domain

2N7A の概要

• エントリーDOI: 10.2210/pdb2n7a/pdb
• 関連するPDBエントリー: 2N7B
• NMR情報: BMRB: 25798
• 分子名称: Sialic acid-binding Ig-like lectin 8 (1 entity in total)
• 機能のキーワード: sialic acid-binding immunoglobulin-like lectin 8, siglec8, saf-2, i-type lectin, carbohydrate-binding receptor, structural protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q9NYZ4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16665.46

構造登録者

Proepster, J.M.,Yang, F.,Rabbani, S.,Ernst, B.,Allain, F.H.-T.,Schubert, M. (登録日: 2015-09-07, 公開日: 2016-07-06, 最終更新日: 2024-11-20)

主引用文献

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

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: 27357658
DOI: 10.1073/pnas.1602214113

実験手法

SOLUTION NMR