Structural requirements of heparin binding to Chlamydia trachomatis.
Heparin is a functional and structural analog of the Chlamydia trachomatis heparan sulfate-like attachment ligand that mediates infectivity by bridging chlamydiae to eukaryotic cells. The binding of heparin to the Chlamydia organism's surface was characterized by a direct binding assay. Although for two C. trachomatis biovars the binding by heparin was saturable, trachoma biovar organisms bound twice the amount of heparin than lymphogranuloma venereum biovar organisms. To prove the structural nature of the heparan sulfate-like ligand interactions, a range of heparin-derived oligosaccharides and sulfation-modified species of heparin were compared for their ability to compete with [3H]heparin for binding to chlamydial organisms and for inhibition of chlamydial attachment and infection of eukaryotic host cells. The assays revealed that a decasaccharide was the minimal chain length required to effectively bind C. trachomatis organisms, compete with the host cell receptor and rescue infectivity. In addition, a moderately sulfated adhesin analog, N-desulfated, N-acetylated heparin, was able to compete with chlamydial organisms for host cell receptors, whereas this derivative could not compete with [3H]heparin for binding to chlamydial organisms. These results indicate that the specificity of the eukaryotic cell receptor and the chlamydial surface acceptor differ in their fine-structure requirements of ligand binding, and that the size and sulfation density of the heparan sulfate-like ligand each contribute to its ability to bind and bridge chlamydiae to eukaryotic cells.
Chen
J C
JC
Department of Laboratory Medicine, University of California, San Francisco 94143, USA.
Zhang
J P
JP
Stephens
R S
RS
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000378:metabolism* / Q000472:pathogenicity; D016264:Dextran Sulfate / Q000494:pharmacology; D006367:HeLa Cells; D006493:Heparin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D014316:Tritium
D016264:Dextran Sulfate; D006493:Heparin; D006497:Heparan Sulfate; D011956:Receptors, Cell Surface; D013462:Sulfur Radioisotopes; D014316:Tritium; C037680:heparin receptor