title: Extended N-sulfated domains reside at the nonreducing end of heparan sulfate chains.
abstract: Heparan sulfate (HS) serves as a cell-surface co-receptor for growth factors, morphogens, and chemokines. These HS and protein binding events depend on the fine structure and distribution of domains along an HS chain. A given domain can vary in terms of uronic acid epimer, N- and O-sulfate, and N-acetate content. The most highly sulfated regions of HS chains, N-sulfated (NS) domains, play prominent roles in HS and protein binding. We have analyzed HS oligosaccharides from various mammalian sources and provide evidence that NS domains residing at the nonreducing end (NRE) are, on average, longer than those residing in the internal regions of the chain. Additionally, they are more highly sulfated than their internal counterparts. These features are independent of the sulfation pattern of the bulk HS chains. From disaccharide analysis, it is clear that NS domains do not always occupy HS NREs. However, when they do, they tend to terminate in a subset of N-sulfated disaccharides. Our observations are consistent with a significant role of NRE NS domains in HS-growth factor interactions.
authors.affiliation: Department of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Gregory O
authors.initials: GO
authors.lastname: Staples
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Shi
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
mesh_terms: D000818:Animals; D002417:Cattle; D002853:Chromatography, Liquid / Q000379:methods; D004187:Disaccharides / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013431:Sulfates / Q000737:chemistry
chemical_list: D004187:Disaccharides; D006497:Heparan Sulfate; D009844:Oligosaccharides; D013431:Sulfates