Liu Yanshun, Eisenberg David
Howard Hughes Medical Institute, UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Department of Chemistry and Biochemistry and Biological Chemistry, University of California, Los Angeles, California 90095, USA.
Protein Sci. 2002 Jun;11(6):1285-99. doi: 10.1110/ps.0201402.
Three-dimensional (3D) domain swapping creates a bond between two or more protein molecules as they exchange their identical domains. Since the term '3D domain swapping' was first used to describe the dimeric structure of diphtheria toxin, the database of domain-swapped proteins has greatly expanded. Analyses of the now about 40 structurally characterized cases of domain-swapped proteins reveal that most swapped domains are at either the N or C terminus and that the swapped domains are diverse in their primary and secondary structures. In addition to tabulating domain-swapped proteins, we describe in detail several examples of 3D domain swapping which show the swapping of more than one domain in a protein, the structural evidence for 3D domain swapping in amyloid proteins, and the flexibility of hinge loops. We also discuss the physiological relevance of 3D domain swapping and a possible mechanism for 3D domain swapping. The present state of knowledge leads us to suggest that 3D domain swapping can occur under appropriate conditions in any protein with an unconstrained terminus. As domains continue to swap, this review attempts not only a summary of the known domain-swapped proteins, but also a framework for understanding future findings of 3D domain swapping.
三维（3D）结构域交换是指两个或多个蛋白质分子在交换其相同结构域时形成一种连接。自从“3D结构域交换”一词首次用于描述白喉毒素的二聚体结构以来，结构域交换蛋白的数据库已大幅扩展。对目前约40个已进行结构表征的结构域交换蛋白案例的分析表明，大多数交换的结构域位于N端或C端，并且这些交换的结构域在一级和二级结构上具有多样性。除了将结构域交换蛋白制成表格外，我们还详细描述了几个3D结构域交换的例子，这些例子展示了蛋白质中多个结构域的交换、淀粉样蛋白中3D结构域交换的结构证据以及铰链环的灵活性。我们还讨论了3D结构域交换的生理相关性以及3D结构域交换的可能机制。目前的知识状况使我们认为，在适当条件下，任何具有无约束末端的蛋白质都可能发生3D结构域交换。随着结构域不断进行交换，本综述不仅试图总结已知的结构域交换蛋白，还试图构建一个框架来理解3D结构域交换的未来研究结果。
