PDBsum entry 2n7b

Structural protein

PDB id: 2n7b

Contents

Protein chain

145 a.a.

Ligands

NAG-G6S-SIA-FUC

0D8

PDB id:

2n7b

Name:

Structural protein

Title:

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

Structure:

Sialic acid-binding ig-like lectin 8. Chain: a. Fragment: n-terminal lectin domain (unp residues 17-155). Synonym: siglec-8, sialoadhesin family member 2, saf-2. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Variant: siglec8. Gene: siglec8, saf2. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

J.M.Proepster,F.Yang,S.Rabbani,B.Ernst,F.H.-T.Allain,M.Schubert

Key ref:

J.M.Pröpster et al. (2016). Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8. Proc Natl Acad Sci U S A, 113, E4170. PubMed id: 27357658 DOI: 10.1073/pnas.1602214113

Date:

07-Sep-15 Release date: 06-Jul-16

Protein chain

Q9NYZ4  (SIGL8_HUMAN) -  Sialic acid-binding Ig-like lectin 8 from Homo sapiens

Seq: 499 a.a.

Struc: 145 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1073/pnas.1602214113

Proc Natl Acad Sci U S A 113:E4170 (2016)

PubMed id: 27357658

Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8.

J.M.Pröpster, F.Yang, S.Rabbani, B.Ernst, F.H.Allain, M.Schubert.

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.