2.50
Hdl Handle:
http://hdl.handle.net/10541/109743
Title:
Molecular organization of heparan sulphate from human skin fibroblasts.
Authors:
Turnbull, Jeremy E; Gallagher, John T
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.
Affiliation:
Department of Clinical Research, University of Manchester, Christie Hospital and Holt Radium Institute, U.K.
Citation:
Molecular organization of heparan sulphate from human skin fibroblasts. 1990, 265 (3):715-24 Biochem. J.
Journal:
Biochemical Journal
Issue Date:
1-Feb-1990
URI:
http://hdl.handle.net/10541/109743
PubMed ID:
2137690
Type:
Article
Language:
en
ISSN:
0264-6021
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorTurnbull, Jeremy Een
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2010-08-17T11:26:17Z-
dc.date.available2010-08-17T11:26:17Z-
dc.date.issued1990-02-01-
dc.identifier.citationMolecular organization of heparan sulphate from human skin fibroblasts. 1990, 265 (3):715-24 Biochem. J.en
dc.identifier.issn0264-6021-
dc.identifier.pmid2137690-
dc.identifier.urihttp://hdl.handle.net/10541/109743-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshCarbohydrate Sequence-
dc.subject.meshCells, Cultured-
dc.subject.meshChromatography, Gel-
dc.subject.meshChromatography, Ion Exchange-
dc.subject.meshElectrophoresis, Polyacrylamide Gel-
dc.subject.meshFibroblasts-
dc.subject.meshGlycosaminoglycans-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshHumans-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMolecular Structure-
dc.subject.meshOligosaccharides-
dc.subject.meshSkin-
dc.titleMolecular organization of heparan sulphate from human skin fibroblasts.en
dc.typeArticleen
dc.contributor.departmentDepartment of Clinical Research, University of Manchester, Christie Hospital and Holt Radium Institute, U.K.en
dc.identifier.journalBiochemical Journalen
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