Characterizing the non-reducing end structure of heparan sulfate.
The reducing end of heparan sulfate has been known for a long time, but information on the non-reducing end has been lacking. Recent studies indicate that the non-reducing end of heparan sulfate might be the place where fibroblast growth factor signaling complex forms. The non-reducing end also changes with heparanase digestion and, thus, might serve as a marker for tumor pathology. Using high performance liquid chromatography-coupled mass spectrometry, we have identified and characterized the non-reducing end of bovine kidney heparan sulfate. We find that the non-reducing end region is highly sulfated and starts with a glucuronic acid (GlcA) residue. The likely sequence of the non-reducing end hexasaccharides is GlcA-GlcNS6S-UA+/-2S-GlcNS+/-6S-Ido2S-GlcNS+/-6S (where GlcNS is N-sulfate-D-glucosamine, S is sulfate, UA is uronic acid, and Ido is iduronic acid). Our data suggests that the non-reducing end of bovine kidney heparan sulfate is not trimmed by heparanase and is capable of supporting fibroblast growth factor signaling complex formation.
Wu
Zhengliang L
ZL
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Lech
Miroslaw
M
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D005346:Fibroblast Growth Factors / Q000502:physiology*; D020723:Glucuronic Acid / Q000737:chemistry; D005966:Glucuronidase / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry*; D007668:Kidney / Q000737:chemistry; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D015398:Signal Transduction; D000099175:Heparanase
D005346:Fibroblast Growth Factors; D020723:Glucuronic Acid; D005966:Glucuronidase; D006497:Heparan Sulfate; D000099175:Heparanase