Minimal heparin/heparan sulfate sequences for binding to fibroblast growth factor-1
Minimal heparin/heparan sulfate sequences for binding to fibroblast growth factor-1
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DOI：
10.1006/bbrc.2002.6634
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发表时间：
2002-03-22
影响因子：
3.1
通讯作者：
Casu, B
中科院分区：
文献类型：
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作者：
Guerrini, M;Agulles, T;Casu, B
糖胺聚糖类肝素和硫酸乙酰肝素（HS）与成纤维细胞生长因子FGF 1结合并促进其二聚化，这是结合细胞受体并触发促有丝分裂信号的先决条件。通过表面等离子体共振（SPR）、NMR光谱和MALDI质谱研究，使用三种合成的四糖GlcNSO（3）60 R-IdoA 2SO（3）-GleNSO（3）60 R '-IdoA 2SO（3）OPr，来解决肝素/HS序列结合FGF 1的最小结构要求的问题（AA，R = R' = SO 3; BA，R = H，R' = SO 3; BB，R = R' = H; Pr，丙基）。AA和BA显着相互作用的蛋白质，而BB几乎是无活性的。NNR光谱表明，AA的相互作用主要涉及其非还原端的GlcNSO（3）6SO（3）IdoA 2SO（3）二糖部分，而非还原侧（NR）和还原侧（R）的残基似乎都参与了BA的较弱复合物。此外，MALDI实验表明，除了1：1蛋白质：四糖复合物之外，AA和BA能够形成2：1复合物，表明肝素/HS诱导的FGF 1二聚化仅需要每个四糖一个6-OSO 3基团。(C)2002 Elsevier Science（美国）。
The glycosaminoglyeans heparin and heparan sulfate (HS) bind to fibroblast growth factor FGF1 and promote its dimerization, a proposed prerequisite for binding to a cellular receptor and triggering mitogenic signals. The problem of minimal structural requirements for heparin/HS sequences to bind FGF1 was approached by surface plasmon resonance (SPR), NMR spectroscopy, and MALDI mass spectrometry studies using the three synthetic tetrasaccharides GlcNSO(3)60R-ldoA2SO(3)-GleNSO(3)60R'-IdoA2SO(3)OPr (AA, R = R' = SO3; BA, R = H, R' = SO3; BB, R = R' = H; Pr, propyl). AA and BA significantly interact with the protein, whereas BB is practically inactive. The NNR spectra show that, whereas the interaction of AA primarily involves the GlcNSO(3)6SO(3)IdoA2SO(3) disaccharide moiety at its nonreducing end, residues at both the nonreducing (NR) and reducing side (R) appear to be involved in the weaker complex of BA. Furthermore, MALDI experiments show that, in addition to 1:1 protein:tetrasaccharide complexes, AA and BA are able to form 2:1 complexes, indicating that heparin/ HS-induced dimerization of FGF1 requires only one 6-OSO3 group per tetrasaccharide. (C) 2002 Elsevier Science (USA).