Year: 2001
Type: review
Abstract: HS binds to many proteinsHS proteoglycans on cell surfaces, in basement membranes, or in cartilage (see Figure 1) influence biological processes by interacting with a large number of physiologically important macromolecules.The HS polysaccharide chains of the proteoglycans, covalently attached to different core proteins, carry negatively charged sulfate groups, whose position on the disaccharide building blocks of the polysaccharide (Nacetylglucosamine-hexuronic acid; see Esko and Lindahl, this Perspective series, ref. 1) contributes to the specificity of the interactions.Many signaling molecules, such as FGFs, VEGF, TGF-β1 and -β2, as well as several chemokines and cytokines, bind to HS present on cell surface proteoglycans (2) (see Figure 1).As first demonstrated for FGFs, the proteoglycans act as coreceptors for the signaling molecules (see ref.3).In addition, ECM proteins, proteases, protease inhibitors, lipases, lipoproteins, and microbial proteins are known to show affinity for HS.The pharmacologically important interaction between the protease inhibitor antithrombin and heparin (a highly sulfated variant of HS), which results in inhibition of blood coagulation, depends on several essential sulfate groups (4).In particular, the 3-O-sulfate group of the glucosamine residue in the middle of the interacting pentasaccharide sequence contributes greatly to the high-affinity binding between the polysaccharide and the protein.The interaction results in a conformational change in antithrombin, which now becomes a much more efficient inhibitor of blood coagulation.Signaling of bFGF (FGF-2) through its receptor will not occur without binding of the growth factor to HS.In this case, 2-Osulfate groups of iduronic acid residues have been shown to be part of the interacting saccharide sequence (see Gallagher, this Perspective series, ref. 5).
DOI: 10.1172/jci13561
Authors: Erik Forsberg, Lena Kjellén
Institution: Uppsala University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1966259416