Heparin, sulfated heparinoids, and lipoteichoic acids bind to the 70-kDa peptidoglycan/lipopolysaccharide receptor protein on lymphocytes.
The same 70-kDa protein, present on the surface of mouse lymphocytes, served as the predominant binding site for heparin, heparinoids, and bacterial lipoteichoic acids, as well as peptidoglycan and lipopolysaccharides. This conclusion was supported by the following results: (a) all of these compounds photoaffinity cross-linked to one major 70-kDa 6.5-7.0 pI protein that co-migrated on two-dimensional polyacrylamide gel electrophoresis; (b) peptide maps of the 70-kDa proteins digested with chymotrypsin, subtilisin, protease V, or papain yielded the same peptides for heparin-, lipoteichoic acid-, peptidoglycan-, and lipopolysaccharide-binding proteins; (c) cross-linking of peptidoglycan, lipopolysaccharide, lipoteichoic acid, and heparin was competitively inhibited by the same compounds with the same order of potency, i.e. carboxyl-reduced sulfated heparin > peptidoglycan > pentosan polysulfate > heparin > chitin > dextran sulfate > trestatin sulfate > polyanetholesulfonate > fucoidan > beta-cyclodextrin tetradecasulfate > heparan sulfate > carrageenan lambda > lipoteichoic acids > Re-lipopolysaccharide > lipopolysaccharide > lipid A > polygalacturonic acid; and (d) cross-linking of each of these ligands was not inhibited by carboxyl-reduced heparin, dextran, beta-cyclodextrin, trestatin, carrageenan kappa, chondroitin 4-sulfate, chondroitin 6-sulfate, beta-D-glucan, carboxy-methylcellulose, levan, alpha-D-mannan, and glycogen. The minimum size of the molecule that bound was 7-9 glycan residues, whereas, di- and trisaccharides did not bind. There was a logarithmic linear relationship between the strength of the binding and the length of the polymer (up to > 1500 glycan residues), which indicates an avidity effect of the cooperative binding of one polymeric molecule to several receptor molecules on the cell surface. The 70-kDa receptor, therefore, has a broad, but limited specificity of binding for non-charged (peptidoglycan and chitin), highly negatively charged (heparin and heparinoids), and weakly negatively charged (lipoteichoic acids, lipopolysaccharides, and lipid A) ligands.
Dziarski
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R
Northwest Center for Medical Education, Indiana University School of Medicine, Gary 46408.
Gupta
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D
D000209:Acute-Phase Proteins; D000595:Amino Acid Sequence; D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D006493:Heparin / Q000302:isolation & purification / Q000378:metabolism*; D006497:Heparan Sulfate / Q000302:isolation & purification / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D011134:Polysaccharides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013682:Teichoic Acids / Q000302:isolation & purification / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D006493:Heparin; D006497:Heparan Sulfate; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D013682:Teichoic Acids; D000099231:Lipopolysaccharide-Binding Protein; C051223:peptidoglycan receptor; C009900:lipoteichoic acid