Glycosaminoglycans: Structure and Biological Functions

Abstract

Glycosaminoglycans are among the most complex polysaccharide chains that are either covalently linked to protein cores (to form proteoglycans) or free as unsulfated hyaluronan. They exist associated with virtually all cell surfaces and extracellular matrices of higher organisms, where their fine structure facilitates interactions with proteins, which underlie their myriad biological functions.

Keywords: glycosaminoglycans; proteoglycans; glycosaminoglycan‐protein interactions; mucopolysaccharidosis; heparin

Figure 1.

Structural features underlying GAG–protein interactions. (a) ATIII‐binding sequence in HN, moieties critical to binding are shown in red. (b) HN‐binding sequence in ATIII is in an α‐helical region containing a sequence rich in basic amino acids (shown in red and green), asterisk denotes position of residue number 125 (adapted from Jackson et al., ). (c) (Upper left panel) Electron micrograph of procollagen molecules (each ∼300 nm) with globular C‐termini; (lower left panel) HN‐gold binds near procollagen N‐terminus, and (right panel) crosslinks two procollagens at binding site. Sequence proposed as the HN‐binding domain of type I collagen begins at lysine residues (shown in red) located at position 87 from the N‐terminus, is composed of three chains and is rich in basic amino acids (shown in red and green). Artwork by Drew Likens.

Figure 2.

Intracellular and extracellular actions of GAGs. (a) Some proposed intracellular activities of GAGs. (b) Electron micrograph of the substantia propria of human cornea showing cross and longitudinal sections of collagen fibrils; GAGs occupy interfibrillar spaces (magnification × 90 000). (c) (Top) PG and integrin‐mediated cell adhesion to matrix; (bottom) model for disruption of cell‐matrix interactions by GAG. (d) Left: carotid artery with restenosis‐like response after endothelial denudation; right: carotid artery exposed following injury to HN. Reprinted with permission of the American Heart Association from Guyton et al., . Artwork in (c) by Shawn M. Sweeney.

Figure 3.

Defects of GAG catabolism cause the mucopolysaccharidosis (MPS) disorders in humans and animals. (a) Clinical features of a 10‐year‐old child with MPS I. Note the depressed bridge of the nose, wide‐spaced eyes, low‐set ears and coarse facial features. She is unable to fully extend her fingers. (b) Two steps in the lysosomal catabolism pathway of HS; further steps exist but are not shown (adapted from Neufeld and Meunzer, ). (c) Clinical features of MPS VII in the dog. The dog on the right cannot stand or walk at 6 months of age. He has low‐set ears, wide‐spaced eyes with corneal clouding and tearing, and malformed ribs. The dog on the left also has MPS VII but received a heterologous bone marrow transplant at 6 weeks of age and continued to stand and walk for 6 years, and had diminished facial dysmorphia, corneal clouding, and rib malformations. The authors gratefully acknowledge Sallie Martinez of Escondido California for the photograph in (a), and Dr Mark Haskins, School of Veterinary Medicine, University of Pennsylvania, for the photograph in (c), which includes unpublished data from his research. Artwork by Drew Likens.

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References

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Further Reading

Conrad HE (1998) Heparin‐Binding Proteins. San Diego, CA: Academic Press.

Esko JD, Rostand KS and Weinke JL (1988) Tumor formation dependent on proteoglycan biosynthesis. Science 241: 1092–1096.

Haskins ME and Giger U (1997) Lysosomal storage diseases. In: Kaneko JJ, Harvey JW and Bruss ML (eds) Clinical Biochemistry of Domestic Animals, 5th edn, pp. 741–761. New York: Academic Press.

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Ottlinger ME, Pukac LP and Karnovsky MJ (1993) Heparin inhibits mitogen‐activated protein kinase activation in intact rat vascular smooth muscle cells. Journal of Biological Chemistry 268: 19173–19176.

San Antonio JD, Lander AD, Karnovsky MJ and Slayter HS (1994) Mapping the heparin‐binding sites on type I collagen monomers and fibrils. Journal of Cell Biology 125: 1179–1188.

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Antonio, James D San, and Iozzo, Renato V(Apr 2001) Glycosaminoglycans: Structure and Biological Functions. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000704]