Three-dimensional solution structure of a unique S100 protein.
Three-dimensional solution structure of a unique S100 protein.
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独特的 S100 蛋白质的三维溶液结构。
DOI：
10.1016/j.bbrc.2005.08.005
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Yu,Chin
中科院分区：
文献类型：
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作者：
Sivaraja,Vaithiyalingam;Kumar,ThallapuranamKrishnaswamySuresh;Prudovsky,Igor;Yu,Chin
S100 A13是属于EF-手型Ca 2+结合蛋白的S100亚家族的同源二聚体蛋白。S100 A13具有独特的物理和功能特性，在S100家族的其他成员中没有观察到。S100 A13对于酸性成纤维细胞生长因子（FGF-1）的非经典输出至关重要，其在其N-末端缺乏信号肽。在本研究中，我们报告的三维溶液结构的Ca 2+结合的S100 A13使用各种3D NMR实验。S100 A13的结构是球状的，每个亚基中有四个螺旋和一个反平行的β折叠。二聚体界面主要由螺旋H1、H1′、H4和H4′的反平行排列形成。等温滴定量热法（ITC）实验表明，S100 A13非协同结合四个钙离子。S100 A13和其他S100蛋白的三维结构之间存在显著差异。S100 A13中不存在对其他S100蛋白中蛋白质-蛋白质相互作用有很大贡献的疏水口袋。S100 A13的结构的特征在于由位于C-末端的带正电荷的残基在很大程度上贡献的密集的阳离子簇两侧的带负电荷的残基的大补丁。ITC实验的结果显示，缺少C-末端区段（残基88-98）的S100 A13不能结合FGF-1。S100 A13的三维结构不仅提供了有用的线索，它在非经典的信号肽的蛋白质，如FGF-1的输出的作用，但也铺平了道路，合理设计的药物，对FGF诱导的肿瘤。
S100A13 is a homodimeric protein that belongs to the S100 subfamily of EF-hand Ca2+-binding proteins. S100A13 exhibits unique physical and functional properties not observed in other members of the S100 family. S100A13 is crucial for the non-classical export of acidic fibroblast growth factors (FGFs-1), which lack signal peptide at their N-terminal end. In the present study, we report the three-dimensional solution structure of Ca2+-bound S100A13 using a variety of 3D NMR experiments. The structure of S100A13 is globular with four helices and an antiparallel β-sheet in each subunit. The dimer interface is formed mainly by an antiparallel arrangement of helices H1, H1′, H4, and H4′. Isothermal titration calorimetry (ITC) experiments show that S100A13 binds non-cooperatively to four calcium ions. Prominent differences exist between the three-dimensional structures of S100A13 and other S100 proteins. The hydrophobic pocket that largely contributes to protein–protein interactions in other S100 proteins is absent in S100A13. The structure of S100A13 is characterized by a large patch of negatively charged residues flanked by dense cationic clusters contributed largely by the positively charged residues located at the C-terminal end. Results of ITC experiments reveal that S100A13 lacking the C-terminal segment (residues 88–98) fails to bind FGF-1. The three-dimensional structure of S100A13 not only provides useful clues on its role in the non-classical export of signal peptide-less proteins such as FGF-1 but also paves the way for rational design of drugs against FGF-induced tumors.