Design of three-dimensional domain-swapped dimers and fibrous oligomers
Design of three-dimensional domain-swapped dimers and fibrous oligomers
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DOI：
10.1073/pnas.98.4.1404
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发表时间：
2001-02-13
影响因子：
11.1
通讯作者：
Eisenberg, D
中科院分区：
文献类型：
--
作者：
Ogihara, NL;Ghirlanda, G;Eisenberg, D
三维（3D）结构域交换蛋白质是单体蛋白质的分子间折叠类似物;两者都通过相同的相互作用稳定，但单个结构域在单体蛋白质中分子内相互作用，而它们在3D结构域交换结构中形成分子间相互作用。几种结构域交换的二聚体和三聚体的结构和形成条件是已知的，但是更高级的3D结构域交换的低聚物的形成还没有被彻底研究。在这里，我们对比结构域交换的结构后果，从两个设计的三螺旋束：一个与上-下-上拓扑结构，另一个与上-下-下拓扑结构。上-下-上拓扑结构产生了结构域交换的二聚体，其结构已通过X射线晶体学确定为1.5埃分辨率。相比之下，结构域交换的蛋白质与向上-向下-向下拓扑结构形成原纤维，如电子显微镜和动态光散射所示。这表明设计原理可以预测3D结构域交换分子的寡聚状态，这应该有助于结构域交换蛋白质和生物材料的设计。
Three-dimensional (3D) domain-swapped proteins are intermolecularly folded analogs of monomeric proteins; both are stabilized by the identical interactions, but the individual domains interact intramolecularly in monomeric proteins, whereas they form intermolecular interactions in 3D domain-swapped structures. The structures and conditions of formation of several domain-swapped dimers and trimers are known, but the formation of higher order 3D domain-swapped oligomers has been less thoroughly studied. Here we contrast the structural consequences of domain swapping from two designed three-helix bundles: one with an up-down-up topology, and the other with an up-down-down topology. The up-down-up topology gives rise to a domain-swapped dimer whose structure has been determined to 1.5 Angstrom resolution by x-ray crystallography. In contrast, the domain-swapped protein with an up-down-down topology forms fibrils as shown by electron microscopy and dynamic light scattering. This demonstrates that design principles can predict the oligomeric state of 3D domain-swapped molecules, which should aid in the design of domain-swapped proteins and biomaterials.