Abstract
Sialoadhesin is a sialic acid-binding immunoglobulin-like lectin (Siglec), expressed on subsets of macrophages. It is a model system for Siglec receptor-mediated cell surface interactions through binding of sialylated glycoconjugates. The N-terminal sialoadhesin domain can mediate sialic acid-binding on its own. The structure of this domain has been determined in complex with a sialic acid-containing heptapeptide, (Ala-Gly-His-Thr(Neu5Ac)-Trp-Gly-His). The affinity of sialoadhesin for this ligand is four times higher than the affinity for the natural linkage 2,3'-sialyllactose. The structure of the glycopeptide complex suggests strategies for ligand optimization and provides possible explanations for the observed differences in specificities among the Siglecs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / metabolism
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Cricetinae
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Crystallography, X-Ray
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Glycopeptides / chemistry*
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Glycopeptides / metabolism
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Humans
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Ligands
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Macromolecular Substances
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / metabolism
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Mice
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Models, Molecular
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Protein Structure, Tertiary*
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Receptors, Immunologic / chemistry*
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Receptors, Immunologic / metabolism
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Sialic Acid Binding Ig-like Lectin 1
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Sialic Acids / metabolism
Substances
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Cell Adhesion Molecules
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Glycopeptides
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Ligands
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Macromolecular Substances
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Membrane Glycoproteins
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Receptors, Immunologic
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SIGLEC1 protein, human
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Sialic Acid Binding Ig-like Lectin 1
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Sialic Acids
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Siglec1 protein, mouse