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S-9-1 Some observations on the structure and function of heparan sulphate
John T Gallagher, Paterson Institute, Manchester M20 4BX, England

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@Heparan sulphate (HS) is a complex linear polysaccharide found mainly in association with cell surfaces and the pericellular matrix. It is normally present as a component of proteoglycans (PGs) and the core proteins of the HSPGs largely determine the cell and tissue distribution. One of the major functions of HS is to act as a co-receptor for a variety of growth factors and cytokines; it also plays key roles in other processes unrelated to cell growth such as the control of blood coagulation and the regulation of lipid metabolism. HS is also an important molecule in the control of cell adhesion. This functional diversity of HS arises because of its capacity for specific protein recognition with consequent modulation of activity of the interacting proteins. The most extensively documented example of this is the activation of antithrombin by a rare pentasaccharide sequence present in HS and in the chemically related therapeutic heparins. Other examples of binding specificity or selectivity include interactions with basic fibroblast growth factor (bFGF), hepatocyte growth factor, fibronectin and cytokines such as interferon , platelet factor 4 and IL-8.

@Implicit in the realization of this extensive functional repertoire of HS is the presence of distinct intra-chain sequences or conformations that support the range of required protein interactions. This appears to be achieved by the unique molecular design of HS in which the sulphated sugar residues are clustered in a series of domains, called S-domains, of variable length and sulphation pattern separated by regions of low sulphation and relatively uniform structure. Information for protein recognition is present mainly within the hypervariable S-domains and, in the cases of multimeric proteins (eg. platelet factor 4) the spacing of these domains along The polymer chain. New approaches to the sequence analysis of the S-domains in HS will be described and ideas about how HS regulates cell proliferation will be discussed in relation to growth factors such as bFGF and VEGF that act on vascular cells.

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