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.
Department of Chemistry, The Carlsberg Laboratory, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
Jens T
JT
Bukrinsky
Phaedria M
PM
St Hilaire
Morten
M
Meldal
Paul R
PR
Crocker
Anette
A
Henriksen
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