Dataset Information

Binding of hyaluronate and chondroitin sulphate to liver endothelial cells.

ABSTRACT: Hyaluronate is taken up and metabolized in liver endothelial cells by means of a receptor. To characterize the interaction with the receptor, two preparations of 3H-labelled hyaluronate, of Mr 4 X 10(5) and 6.4 X 10(6), and a series of hyaluronate oligosaccharides were bound to cultured liver endothelial cells at 7 degrees C. The dissociation constant varied between 4.6 X 10(-6) M for an octasaccharide and 9 X 10(-12) M for the largest polymer. The Mr-dependence for the series of oligosaccharides was explained by the increased probability of binding due to the repetitive sequence along the chain. The high affinity of high-Mr hyaluronate for the receptor could also be mainly ascribed to this effect, which rules out any major contribution of co-operative multiple-site attachment to the cell surface. Each liver endothelial cell can bind 10(5) oligosaccharides, about 10(4) molecules with Mr 4 X 10(5) and about 10(3) molecules with Mr 6.4 X 10(6). This is explained by mutual exclusion of large molecules from the cell surface. Chondroitin sulphate is also bound to liver endothelial cells. Inhibition studies showed that it binds to the same receptor as hyaluronate and with an affinity that is about 3-fold higher than that of hyaluronate of the same degree of polymerization.

SUBMITTER: Laurent TC

PROVIDER: S-EPMC1146621 | biostudies-other | 1986 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundPlacental malaria is typified by selective clustering of Plasmodium falciparum in the intervillous blood spaces of the placenta. Sequestration of malaria parasite in the human placenta is mediated by interactions between chondroitin sulphate A (CSA) on the syncytiotrophoblasts and proteins expressed on the surface of infected human erythrocytes. Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) encoded by the var2CSA gene is believed to be the main parasite ligand for CSA-mediated placental binding.MethodsExtensive sequence and structure comparisons of the various CSA-binding and non-binding DBL domains from the var2CSA gene from A4 and 3D7 strains of P. falciparum were performed. Three-dimensional structural models of various DBL domains were built and analysed with a view to assessing conservation of CSA interaction sites across various DBL domains.ResultsEach of the six DBL domains from var2CSA are likely to retain the disulfide linkages evident from previously published DBL domain crystal structures. The number of disulfide linkages between the various DBL domains analysed varies from three to seven, of which two are conserved across all DBL domains. The conserved disulfide linkages are distributed within the respective three sub-domains and only one linkage is shared by sub-domains I and II. Major differences between CSA-binding DBL domains are in the loop regions, which tie the alpha helices together, and in variable length terminal extensions. Intriguingly, a crucial loop from A4 DBL 3X which provides the important Gly and Lys residues that chelate the bound sulphate is missing or significantly altered in all other DBL domains that interact with CSA. Further analysis of the proposed sulphate and predicted CSA-binding site indicates either none or very low level of conservation among the critical interacting residues.ConclusionStructural comparisons of the three-dimensional structures of CSA-binding DBL domains indicates that the proposed CSA interaction site on A4 DBL 3X is unlikely to be conserved across the other CSA-binding DBL domains from var2CSA. Therefore, the 4 CSA-binding DBL domains encoded by var2CSA are unlikely to have common architectures to their CSA recognition sites. These structural insights have clear implications in using CSA-binding DBL domains for vaccines against placental malaria as it is proposed that the various CSA-binding DBL domains on var2CSA will recognize their CSA ligands differently.

Dataset Information

Binding of hyaluronate and chondroitin sulphate to liver endothelial cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets