Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate.
AffiliationClinical Research Department, Christie Hospital, Manchester, United Kingdom.
MetadataShow full item record
AbstractThe structural properties of fibroblast heparan sulfate (HS) that are necessary for it to bind strongly to basic fibroblast growth factor (bFGF) have been investigated using bFGF affinity chromatography. Specific enzymic and chemical scission of HS, together with chemical N-desulfation, revealed that N-sulfate groups and iduronate-2-sulfates (IdoA(2-OSO3)) were essential for the interaction. bFGF-affinity chromatography of sulfated oligosaccharides released from HS by treatment with heparitinase led to the identification of an oligosaccharide component (oligo-H), seven disaccharides in length, with a similar affinity for bFGF as the parent molecule. Heparinase treatment of this fraction abolished the high affinity binding to bFGF. Analysis of oligo-H indicated that 74% of the disaccharide units had the structure IdoA(2-OSO3)alpha 1,4GlcNSO3; the remainder comprised N-acetylated and N-sulfated units, the majority of which were devoid of O-sulfate groups. Oligo-H was fully degraded to disaccharides by treatment with nitrous acid. These results indicate that the sequence of oligo-H is as shown below. delta GlcA beta 1,4GlcNSO3 alpha 1,4[IdoA(2-OSO3)alpha 1,4GlcNSO3]5 alpha 1, 4IdoA alpha 1,4GlcNAc Sulfated oligosaccharides of similar size but with a lower affinity for bFGF had a reduced concentration of IdoA(2-OSO3) but significant quantities of GlcNSO3(6-OSO3) and GlcNAc(6-OSO3). The data indicate a primary role for contiguous sequences of IdoA(2-OSO3)alpha 1,4GlcNSO3 in mediating the high affinity binding between fibroblast HS and bFGF.
CitationIdentification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. 1992, 267 (15):10337-41 J. Biol. Chem.
JournalJournal of Biological Chemistry
- Specific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor.
- Authors: Walker A, Turnbull JE, Gallagher JT
- Issue date: 1994 Jan 14
- Structure of a heparan sulphate oligosaccharide that binds to basic fibroblast growth factor.
- Authors: Habuchi H, Suzuki S, Saito T, Tamura T, Harada T, Yoshida K, Kimata K
- Issue date: 1992 Aug 1
- Heparan sulfate oligosaccharides require 6-O-sulfation for promotion of basic fibroblast growth factor mitogenic activity.
- Authors: Pye DA, Vives RR, Turnbull JE, Hyde P, Gallagher JT
- Issue date: 1998 Sep 4
- Isolation of the porcine heparin tetrasaccharides with glucuronate 2-O-sulfate. Heparinase cleaves glucuronate 2-O-sulfate-containing disaccharides in highly sulfated blocks in heparin.
- Authors: Yamada S, Murakami T, Tsuda H, Yoshida K, Sugahara K
- Issue date: 1995 Apr 14
- Sequence analysis of heparan sulphate indicates defined location of N-sulphated glucosamine and iduronate 2-sulphate residues proximal to the protein-linkage region.
- Authors: Turnbull JE, Gallagher JT
- Issue date: 1991 Jul 15