Highly sensitive sequencing of the sulfated domains of heparan sulfate.
AffiliationCancer Research Campaign and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom.
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AbstractThe heparan sulfates (HS) are hypervariable linear polysaccharides that act as membrane co-receptors for growth factors, chemokines, and extracellular matrix proteins. In most instances, the molecular basis of protein recognition by HS is poorly understood. We have sequenced 75% of the sulfated domains (S-domains) of fibroblast HS, including all of the major ones. This analysis revealed tight coupling of N- and 2-O-sulfation and a low frequency but precise positioning of 6-O-sulfates, which are required functional groups for HS-mediated activation of the fibroblast growth factors. S-domain sequencing was conducted using a novel and highly sensitive method based on a new way of reading the sequence from high performance liquid chromatography separation profiles of metabolically labeled HS-saccharides following specific chemical and enzymatic scission. The implications of the patterns seen in the sulfated domains for better understanding of the synthesis and function of HS are discussed.
CitationHighly sensitive sequencing of the sulfated domains of heparan sulfate. 1999, 274 (26):18455-62 J. Biol. Chem.
JournalJournal of Biological Chemistry