title: Patterns of sulphation in heparan sulphate: polymorphism based on a common structural theme.
abstract: HS appears to be a well-organised molecule with a domain structure that is apparently unique amongst the GAG family (Gallagher, 1989). Further refinements in sequence analysis are needed to corroborate the simplified model proposed in Fig. 4. It is still not clear why evolution has favoured a structural motif of widely spaced sulphated domains. Presumably, some advantages must accrue to the organism from this design, and one idea, that we have discussed previously, is that the polysaccharide functions as a "template" for the organisation of structural proteins in the ECM and for the binding and presentation of growth factors within the matrix polymer network. The sulphated regions are likely to display considerable conformational versatility as a result of the presence of the iduronate residues, and this property may be very important for the protein-binding properties of the polysaccharides (Casu et al., 1988). Sulphation patterns within these regions could favour oligosaccharide conformations necessary for specific protein interactions. An important question in this context is why different cells express on their surfaces HS with subtle differences in sulphation pattern. Perhaps the polymorphic features of HS are involved in higher-order tissue- and organ-specific mechanisms controlling cellular recognition and morphogenesis. The consistency with which aberrant sulphation of HS is detected in malignant disease (Gallagher and Lyon, 1989) in which cellular recognition and differentiation are impaired, adds some substance to this view.
authors.affiliation: CRC Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, U.K.
authors.forename: J T
authors.initials: JT
authors.lastname: Gallagher
authors.forename: J E
authors.initials: JE
authors.lastname: Turnbull
authors.forename: M
authors.initials: M
authors.lastname: Lyon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D006497:Heparan Sulfate