Investigation of the binding network of IGF-I on the cavity surface of IGFBP4
Investigation of the binding network of IGF-I on the cavity surface of IGFBP4
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DOI：
10.1007/s00894-013-2020-8
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发表时间：
2013-10
影响因子：
2.2
通讯作者：
Xin Chen;Shuyan Zhu;Danhui Duan;Tao Wu;Qi Wang
中科院分区：
文献类型：
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作者：
Xin Chen;Shuyan Zhu;Danhui Duan;Tao Wu;Qi Wang
胰岛素样生长因子结合蛋白（IGFBP）通过IGFBP和IGF的高亲和力复合物控制胰岛素样生长因子（IGFs）的生物活性和分布。为了更深入地了解IGF系统的结合相互作用，采用定点诱变和力驱动解吸方法，通过分子动力学（MD）模拟研究IGFBP4与IGF- i的相互作用机制。在IGF-I中，发现Gly7到Asp12残基是热点，它们主要锚定在IGFBP4的n结构域上。蛋白质的接触面积、蛋白质的形状和大小、结合位点的周围环境、两种蛋白质之间的疏水和静电相互作用作为一个复杂的网络来调节蛋白质-蛋白质相互作用。研究还发现，螺旋的展开在突变体中不是不可避免的，它可以通过仔细选择取代的氨基酸来调节。图IGF-I在IGFBP4空腔表面的结合网络
Insulin-like growth factor-binding proteins (IGFBPs) control bioactivity and distribution of insulin-like growth factors (IGFs) through high-affinity complex of IGFBP and IGF. To get more insight into the binding interaction of IGF system, the site-directed mutagenesis and force-driving desorption methods were employed to study the interaction mechanism of IGFBP4 and IGF-I by molecular dynamics (MD) simulation. In IGF-I, residues Gly7 to Asp12 were found to be the hot spots and they mainly anchored on the N-domain of IGFBP4. The contact area, the shape and size of protein, the surroundings of the binding site, the hydrophobic and electrostatic interaction between the two proteins worked as a complex network to regulate the protein-protein interaction. It was also found that the unfolding of the helix was not inevitable in the mutant, and it could be regulated by careful selection of the substituted amino acid.FigureBinding network of IGF-I on the cavity surface of IGFBP4