Probing the supramodular architecture of a multidomain protein: The structure of syntenin in solution
Probing the supramodular architecture of a multidomain protein: The structure of syntenin in solution
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DOI：
10.1016/j.str.2004.12.014
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发表时间：
2005-02-01
期刊：
影响因子：
5.7
通讯作者：
Derewenda, ZS
中科院分区：
文献类型：
--
作者：
Cierpicki, T;Bushweller, JH;Derewenda, ZS
对多结构域蛋白质功能机制的充分理解依赖于我们对它们在溶液中的超模块结构的了解。这对于X射线晶体学和NMR来说都是一项重要的任务，因为固有的灵活性使这些蛋白质的结晶变得困难，而它们的大小对NMR构成了挑战。在这里，我们描述了协同应用的数据来自X-射线晶体学和NMR残留偶极耦合（RDC），以解决问题的supermodular结构的两个结构域的蛋白质，syntenin。Syntenin是一个32 kDa的分子，含有两个PDZ结构域，并参与细胞膜上的组织。我们表明，PDZ域的相互配置明显不同于在晶体结构中看到的，我们提供的证据表明，N-和C-末端片段的syntenin，迄今假定缺乏有序的结构，包含折叠的结构元素在全长蛋白质中与PDZ串联接触。
Full understanding of the mechanism of function of multidomain proteins is dependent on our knowledge of their supramodular architecture in solution. This is a nontrivial task for both X-ray crystallography and NMR, because intrinsic flexibility makes crystallization of these proteins difficult, while their size creates a challenge for NMR. Here, we describe synergistic application of data derived from X-ray crystallography and NMR residual dipolar couplings (RDCs) to address the question of the supramodular structure of a two-domain protein, syntenin. Syntenin is a 32 kDa molecule containing two PDZ domains and is involved in cytoskeleton-membrane organization. We show that the mutual disposition of the PDZ domains clearly differs from that seen in the crystal structure, and we provide evidence that N- and C-terminal fragments of syntenin, hitherto presumed to lack ordered structure, contain folded structural elements in the full-length protein in contact with the PDZ tandem.