The specificity of interactions between proteins and sulfated polysaccharides.
Sulfated polysaccharides are capable of binding with proteins at several levels of specificity. As highly acidic macromolecules, they can bind non-specifically to any basic patch on a protein surface at low ionic strength, and such interactions are not likely to be physiologically significant. On the other hand, several systems have been identified in which very specific substructures of sulfated polysaccharides confer high affinity for particular proteins; the best-known example of this is the pentasaccharide in heparin with high affinity for antithrombin, but other examples may be taken from the study of marine invertebrates: the importance of the fine structure of dermatan sulfate (DS) to its interaction with heparin cofactor II (HCII), and the involvement of sea urchin egg-jelly fucans in species specific fertilization. A third, intermediate, kind of specific interaction is described for the cell-surface glycosaminoglycan heparan sulfate (HS), in which patterns of sulfate substitution can show differential affinities for cytokines, growth factors, and morphogens at cell surfaces and in the intracellular matrix. This complex interplay of proteins and glycans is capable of influencing the diffusion of such proteins through tissue, as well as modulating cellular responses to them.
Mulloy
Barbara
B
Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, Potter's Bar, Hertfordshire, EN6 3QG, UK. bmulloy@nibsc.ac.uk
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D003871:Dermatan Sulfate / Q000737:chemistry / Q000378:metabolism; D004347:Drug Interactions; D006133:Growth Substances / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012617:Sea Urchins; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism*
D000991:Antithrombins; D006133:Growth Substances; D011134:Polysaccharides; D011506:Proteins; D013431:Sulfates; D003871:Dermatan Sulfate; D006493:Heparin; C007789:fucoidan