Abstract
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.
Highlights
SULFATED POLYSACCHARIDES AS POLYELECTROLYTES: NON-SPECIFIC INTERACTIONSSulfated polysaccharides are found throughout the animal kingdom (Dietrich et al 1989, Medeiros et al 2000) and in some plants
Sulfated fucans constitute an interesting group of polysaccharides; algal fucoidans are complex in structure, though a few studies have found regular repeating structures underlying their heterogeneity
The study of the sulfated glycan side-chains of proteoglycans, the glycosaminoglycans has led recently to a more complex and subtle set of ideas about specificity, in which the differential affinities of proteins for various GAG sequences can affect the action of cytokines at the cell surface and can modulate their diffusion between cells
Summary
Laboratory for Molecular Structure, National Institute for Biological Standards and Control South Mimms, Potter’s Bar, Hertfordshire, EN6 3QG, UK. Manuscript received on May 11, 2005; accepted for publication on May 13, 2005; presented by PAULO A.
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