Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue

被引：52

作者：

Canales, Angeles

Lozano, Rosa

Lopez-Mendez, Blanca

Angulo, Jesus

Ojeda, Rafael

Nieto, Pedro M.

Martin-Lomas, Manuel

Gimenez-Gallego, Guillermo

Jimenez-Barbero, Jesus

机构：

[1] CSIC, Ctr Invest Biol, E-28006 Madrid, Spain

[2] CSIC, Inst Invest Quim, E-41080 Seville, Spain

来源：

FEBS JOURNAL | 2006年 / 273卷 / 20期

关键词：

fibroblast growth factor; heparin-like hexasaccharide; protein-carbohydrate complex;

D O I：

10.1111/j.1742-4658.2006.05474.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF-1) and a specifically designed synthetic heparin hexasaccharide has been determined by NMR spectroscopy. This hexasaccharide can substitute natural heparins in FGF-1 mitogenesis assays, in spite of not inducing any apparent dimerization of the growth factor. The use of this well defined synthetic heparin analogue has allowed us to perform a detailed NMR structural analysis of the heparin-FGF interaction, overcoming the limitations of NMR to deal with the high molecular mass and heterogeneity of the FGF-1 oligomers formed in the presence of natural heparin fragments. Our results confirm that glycosaminoglycans induced FGF-1 dimerization either in a cis or trans disposition with respect to the heparin chain is not an absolute requirement for biological activity.

引用

收藏

页码：4716 / 4727

页数：12

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