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    Molecular organization of heparan sulphate from human skin fibroblasts.

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    Authors
    Turnbull, Jeremy E
    Gallagher, John T
    Affiliation
    Department of Clinical Research, University of Manchester, Christie Hospital and Holt Radium Institute, U.K.
    Issue Date
    1990-02-01
    
    Metadata
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    Abstract
    The molecular structure of human skin fibroblast heparan sulphate was examined by specific chemical or enzymic depolymerization and high-resolution separation of the resulting oligosaccharides and disaccharides. Important features of the molecular organization, disaccharide composition and O-sulphate disposition of this heparan sulphate were identified. Analysis of the products of HNO2 hydrolysis revealed a polymer in which 53% of disaccharide units were N-acetylated and 47% N-sulphated, with an N-/O-sulphate ratio of 1.8:1. These two types of disaccharide unit were mainly located in separate domains. Heparitinase and heparinase scission indicated that the iduronate residues (37% of total hexuronate) were largely present in contiguous disaccharide sequences of variable size that also contained the majority of the N-sulphate groups. Most of the iduronate residues (approx. 70%) were non-sulphated. About 8-10% of disaccharide units were cleaved by heparinase, but only a minority of these originated from contiguous sequences in the intact polymer. Trisulphated disaccharide units [alpha-N-sulpho-6-sulphoglucosaminyl-(1----4)-iduronate 2-sulphate], which are the major structural units in heparin, made up only 3% of the disaccharide units in heparan sulphate. O-Sulphate groups (approx. 26 per 100 disaccharide units) were distributed almost evenly among C-6 of N-acetylglucosamine, C-2 of iduronate and C-6 of N-sulphated glucosamine residues. The results indicate that the sulphated regions of heparan sulphate have distinctive and potentially variable structural characteristics. The high content of non-sulphated iduronate in this heparan sulphate species suggests a conformational versatility that could have important implications for the biological properties of the polymer.
    Citation
    Molecular organization of heparan sulphate from human skin fibroblasts. 1990, 265 (3):715-24 Biochem. J.
    Journal
    Biochemical Journal
    URI
    http://hdl.handle.net/10541/109743
    PubMed ID
    2137690
    Type
    Article
    Language
    en
    ISSN
    0264-6021
    Collections
    All Paterson Institute for Cancer Research

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