Selective binding of the scavenger receptor C-type lectin to Lewisx trisaccharide and related glycan ligands.
The scavenger receptor C-type lectin (SRCL) is an endothelial receptor that is similar in organization to type A scavenger receptors for modified low density lipoproteins but contains a C-type carbohydrate-recognition domain (CRD). Fragments of the receptor consisting of the entire extracellular domain and the CRD have been expressed and characterized. The extracellular domain is a trimer held together by collagen-like and coiled-coil domains adjacent to the CRD. The amino acid sequence of the CRD is very similar to the CRD of the asialoglycoprotein receptor and other galactose-specific receptors, but SRCL binds selectively to asialo-orosomucoid rather than generally to asialoglycoproteins. Screening of a glycan array and further quantitative binding studies indicate that this selectivity results from high affinity binding to glycans bearing the Lewis(x) trisaccharide. Thus, SRCL shares with the dendritic cell receptor DC-SIGN the ability to bind the Lewis(x) epitope. However, it does so in a fundamentally different way, making a primary binding interaction with the galactose moiety of the glycan rather than the fucose residue. SRCL shares with the asialoglycoprotein receptor the ability to mediate endocytosis and degradation of glycoprotein ligands. These studies suggest that SRCL might be involved in selective clearance of specific desialylated glycoproteins from circulation and/or interaction of cells bearing Lewis(x)-type structures with the vascular endothelium.
Coombs
Peter J
PJ
Glycobiology Institute, Department of Biochemistry, University of Oxford, UK.
Graham
Sarah A
SA
Drickamer
Kurt
K
Taylor
Maureen E
ME
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000737:chemistry; D001665:Binding Sites; D016466:CHO Cells; D002241:Carbohydrates / Q000737:chemistry; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D000939:Epitopes / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D005643:Fucose / Q000737:chemistry; D005690:Galactose / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D037181:Lectins, C-Type / Q000737:chemistry*; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008024:Ligands; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012685:Sepharose / Q000737:chemistry; D014312:Trisaccharides / Q000737:chemistry*; D014461:Ultracentrifugation
D037263:Asialoglycoprotein Receptor; D002241:Carbohydrates; D018076:DNA, Complementary; D000939:Epitopes; D006017:Glycolipids; D006023:Glycoproteins; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D008024:Ligands; D009844:Oligosaccharides; D011134:Polysaccharides; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D014312:Trisaccharides; C110530:galactosyl-(1,4)-fucopyranosyl-(1,3)-N-acetylglucosamine; D005643:Fucose; D012685:Sepharose; D005690:Galactose