Complex of sialoadhesin with a glycopeptide ligand.
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.
Bukrinsky
Jens T
JT
Department of Chemistry, The Carlsberg Laboratory, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
St Hilaire
Phaedria M
PM
Meldal
Morten
M
Crocker
Paul R
PR
Henriksen
Anette
A
D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D006224:Cricetinae; D018360:Crystallography, X-Ray; D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids / Q000378:metabolism
D015815:Cell Adhesion Molecules; D006020:Glycopeptides; D008024:Ligands; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids; C571167:Siglec1 protein, mouse