Binding of endostatin to endothelial heparan sulphate shows a differential requirement for specific sulphates.
AuthorsBlackhall, Fiona H
Merry, Catherine L R
Jayson, Gordon C
Gallagher, John T
AffiliationDepartment of Medical Oncology, University of Manchester, Cancer Research UK, Christie Hospital NHS Trust, Manchester M20 4BX, UK.
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AbstractEndostatin is a naturally occurring proteolytic fragment of the C-terminal domain of collagen XVIII. It inhibits angiogenesis by a mechanism that appears to involve binding to HS (heparan sulphate). We have examined the molecular interaction between endostatin and HS from micro- and macrovessel endothelial cells. Two discrete panels of oligosaccharides were prepared from metabolically radiolabelled HS, using digestion with either heparinase I or III, and then examined for their endostatin affinity using a sensitive filter-binding assay. Two types of endostatin-binding regions were identified: one comprising sulphated domains of five or more disaccharides in length, enriched in 6-O-sulphate groups, and the other contained long heparinase I-resistant fragments. In the latter case, evidence from the present study suggests that the binding region encompasses a sulphated domain fragment and a transition zone of intermediate sulphation. The contribution to binding of specific O-sulphate groups was determined using selectively desulphated HS species, namely HS from Hs2st-/- mutant cells, and by comparing the compositions of endostatin-binding and non-binding oligosaccharides. The results indicate that 6-O-sulphates play a dominant role in site selectivity and 2-O-sulphates are not strictly essential.
CitationBinding of endostatin to endothelial heparan sulphate shows a differential requirement for specific sulphates. 2003, 375 (Pt 1):131-9 Biochem. J.
JournalThe Biochemical Journal
- Endothelial and fibroblast cell-derived heparan sulphate bind with differing affinity to basic fibroblast growth factor.
- Authors: Pye DA, Kumar S
- Issue date: 1998 Jul 30
- Non-heparan sulfate-binding interactions of endostatin/collagen XVIII in murine development.
- Authors: Rychkova N, Stahl S, Gaetzner S, Felbor U
- Issue date: 2005 Feb
- Endostatin's heparan sulfate-binding site is essential for inhibition of angiogenesis and enhances in situ binding to capillary-like structures in bone explants.
- Authors: Gaetzner S, Deckers MM, Stahl S, Löwik C, Olsen BR, Felbor U
- Issue date: 2005 Jan
- Decorin endocytosis: structural features of heparin and heparan sulphate oligosaccharides interfering with receptor binding and endocytosis.
- Authors: Hausser H, Kresse H
- Issue date: 1999 Dec 15
- Novel glycosylated forms of human plasma endostatin and circulating endostatin-related fragments of collagen XV.
- Authors: John H, Preissner KT, Forssmann WG, Ständker L
- Issue date: 1999 Aug 10