Heparan sulfate fine structure and specificity of proteoglycan functions

Heparan sulfate chains have markedly heterogeneous structures in which distinct patterns of sulfation determine the binding specificity for ligand proteins. These "fine structures" of heparan sulfate are mainly produced by the regulated introduction of sulfate groups at the N-, 2-O-, 6-O-, and 3-O-positions of the sugar chain. Recent biochemical, histochemical, and genetic studies have demonstrated that different fine structures mediate distinct molecular recognition events to regulate a variety of cellular functions. In this review, we focus on the molecular basis of growth factor control by the sulfation status of heparan sulfate.