Liver heparan sulfate structure. A novel molecular design.
The structure of rat liver heparan sulfate (HS) has been investigated using a combination of (a) chain scission with specific reagents, (b) disaccharide compositional analysis, and (c) end-referenced sequence analysis of the proximal, protein-linked region of the chain. This study reveals that the liver synthesizes a highly sulfated HS species (1.34 sulfates/disaccharide), particularly high in N-sulfation (60%) and 2-O-sulfate content (36%). Approximately half of the latter is found in trisulfated disaccharides, i.e. IdceA(2-OSO3) alpha 1-4GlcNSO3 (6-OSO3). End-referencing methodology established the existence of an extended, unmodified heparan (GlcUA beta 1-4GlcNAc) sequence, 8-11 disaccharides in length, attached to the linkage tetrasaccharide, similar to that found in a number of other HS species. Directly following this is a mixed HexUA1-4GlcNR(6-OSO3) (where GlcNR represents alpha-D-glucosamine with an unspecified N-substituent)-containing sequence of variable length, culminating in the appearance of the first IdceA(2-OSO3) residue approximately 20 disaccharides from the linkage region, i.e. approximately 40% along the length of the chain. The distal 60% of the polysaccharide is highly sulfated (approximately 2 sulfates/disaccharide) and mainly comprises three heparin-like domains, highly enriched in IdceA(2-OSO3) residues. Overall, liver HS qualifies as an extreme member of the HS family, with a considerable proportion of heparin-like structure asymmetrically concentrated to the distal part of the chain.
Lyon
M
M
Cancer Research Campaign, Christie Hospital, Manchester, United Kingdom.
Deakin
J A
JA
Gallagher
J T
JT
D000818:Animals; D002240:Carbohydrate Sequence; D002417:Cattle; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004187:Disaccharides / Q000737:chemistry / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry; D005944:Glucosamine / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D012867:Skin / Q000737:chemistry; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium
D004187:Disaccharides; D005944:Glucosamine; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D009844:Oligosaccharides; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium