Proteoglycans are complex extracellular macromolecules consisting of a multidomain core protein to which is attached one or more glycosaminoglycan (GAG) chains. They are structurally very diverse, due to variations in length and sequence of the core proteins as well as the abundance, distribution and composition of the GAG chains. Core protein components are often arranged in modules, which have structural and functional significance, and the same module may be found in more than one core protein type. A single core protein type may have different GAG substituents and differing roles in different tissues. Proteoglycans have diverse, but often vital functions in a variety of tissue contexts. Genetic studies of proteoglycan core proteins and their modifying enzymes have elucidated numerous heritable diseases and syndromes emanating both from aberrant biosynthetic and degradative processes.

Key Concepts:

  • Glycosaminoglycans (GAG) are linked to proteoglycan core proteins via a limited number of O‐ or N‐glycosyl bonds.

  • Synthesis of GAG chains proceeds by the sequential action of glycosyltransferases that catalyse transfer of a glycosyl unit from a nucleotide sugar donor to a protein or the non‐reducing end of a sugar acceptor.

  • Proteoglycans are abundant components of the extracellular matrix and may be associated with the cell surface.

  • Although there are only six major classes of proteoglycan types, there is great diversity in structure, size and composition.

  • Important functions have been attributed to both the protein backbone and GAG substituents.

  • Proteoglycans modulate numerous molecular interactions, for example, cell–cell signalling.

  • Heritable proteoglycan disorders exhibit a wide range of phenotypes with examples from all clinical specialties.

Keywords: glycosaminoglycans; glycosyltransferases; sulfotransferases; extracellular matrix; chondrodystrophies; mucopolysaccharidoses

Figure 1.

Definition of a proteoglycan; cDNA domain structure and proteoglycan structure are shown. (a) Proteoglycans are complex molecules consisting of a protein core (blue) and one (as in decorin) or many (aggrecan) covalently attached glycosaminoglycan (GAG) chains (grey). GAG chain types include chondroitin/dermatan sulfate (CS/DS), keratan sulfate (KS), heparin/heparan sulfate (HS), and hyaluronate (which is not attached to a protein or sulfated). (b) Schematic diagram of aggrecan mRNA domains (labelled above) that correlate to protein domains (Schwartz et al., ).

Figure 2.

Major repeat units of glycosaminoglycan chains. GAG chains consist of disacharride units composed of an N‐acetyl or N‐sulfated hexosamine and either an uronic acid (glucuronic or iduronic) or galactose. Hyaluronate consists of an uronic acid and hexosamine devoid of sulfate. CS, chondriotin sulfate; HS, heparan sulfate; KS, keratan sulfate.



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Schwartz, Nancy B(Aug 2014) Proteoglycans. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000623.pub3]