Ogihara N L, Ghirlanda G, Bryson J W, Gingery M, DeGrado W F, Eisenberg D
UCLA-DOE Laboratory of Structural Biology and the Department of Chemistry and Biochemistry, P.O. Box 951570, University of California, Los Angeles, CA 90095-1570, USA.
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1404-9. doi: 10.1073/pnas.98.4.1404.
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 A 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.
三维（3D）结构域交换蛋白是单体蛋白的分子间折叠类似物；两者都通过相同的相互作用得以稳定，但各个结构域在单体蛋白中进行分子内相互作用，而在3D结构域交换结构中它们形成分子间相互作用。几种结构域交换二聚体和三聚体的结构及形成条件已为人所知，但高阶3D结构域交换寡聚体的形成尚未得到充分研究。在此，我们对比了来自两个设计的三螺旋束的结构域交换的结构后果：一个具有上下上拓扑结构，另一个具有上下下拓扑结构。上下上拓扑结构产生了一个结构域交换二聚体，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，具有上下下拓扑结构的结构域交换蛋白形成了原纤维，这通过电子显微镜和动态光散射得以证明。这表明设计原则可以预测3D结构域交换分子的寡聚状态，这将有助于结构域交换蛋白和生物材料的设计。
