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A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands.
- Source :
-
Nature communications [Nat Commun] 2020 Oct 09; Vol. 11 (1), pp. 5091. Date of Electronic Publication: 2020 Oct 09. - Publication Year :
- 2020
-
Abstract
- Sialic acid-binding immunoglobulin-type lectins (Siglecs) are immunomodulatory receptors that are regulated by their glycan ligands. The connections between Siglecs and human disease motivate improved methods to detect Siglec ligands. Here, we describe a new versatile set of Siglec-Fc proteins for glycan ligand detection. Enhanced sensitivity and selectivity are enabled through multimerization and avoiding Fc receptors, respectively. Using these Siglec-Fc proteins, Siglec ligands are systematically profiled on healthy and cancerous cells and tissues, revealing many unique patterns. Additional features enable the production of small, homogenous Siglec fragments and development of a quantitative ligand-binding mass spectrometry assay. Using this assay, the ligand specificities of several Siglecs are clarified. For CD33 (Siglec-3), we demonstrate that it recognizes both α2-3 and α2-6 sialosides in solution and on cells, which has implications for its link to Alzheimer's disease susceptibility. These soluble Siglecs reveal the abundance of their glycan ligands on host cells as self-associated molecular patterns.
- Subjects :
- Animals
Antigens, CD genetics
Antigens, CD metabolism
Breast Neoplasms metabolism
CHO Cells
Cricetulus
Female
HEK293 Cells
Humans
Immunoglobulin Fc Fragments genetics
Immunoglobulin Fc Fragments metabolism
Immunoglobulin G genetics
Immunoglobulin G metabolism
K562 Cells
Mass Spectrometry
Polysaccharides metabolism
Sialic Acid Binding Ig-like Lectin 3 metabolism
Sialic Acid Binding Immunoglobulin-like Lectins genetics
Sialic Acid Binding Immunoglobulin-like Lectins isolation & purification
Sialic Acids metabolism
Sialyltransferases genetics
Sialyltransferases metabolism
Spleen cytology
Spleen metabolism
Streptavidin metabolism
Polysaccharides analysis
Sialic Acid Binding Immunoglobulin-like Lectins chemistry
Sialic Acid Binding Immunoglobulin-like Lectins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33037195
- Full Text :
- https://doi.org/10.1038/s41467-020-18907-6