Diabodies are bispecific antibody fragments that have two antigen binding Fv domains. They are unique among hundreds of different formats of bispecific antibodies because they are small and rigid enough to be crystallized. Diabodies are generated by connecting variable regions of heavy and light chains by a peptide linker. Because of the short length of the linker, intramolecular association of the variable regions is not allowed. Instead, the variable regions from the different peptide chains associate together, forming a dimeric complex with two antigen binding sites. Previous crystallographic studies of diabodies demonstrate the extraordinary structural diversity of diabodies. They have also shown that the relative orientation and interaction of the two Fv domains in diabodies have substantial flexibility due to instability of the Fv interface. Introduction of site specific mutations and disulfide bridges can reduce flexibility and therefore increase rigidity and predictability of the diabody structures. These stabilized diabodies will be useful for future application to structural biology and protein nanotechnology.

中文翻译：

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双抗体的结构多样性和灵活性

双抗体是具有两个抗原结合 Fv 结构域的双特异性抗体片段。它们在数百种不同形式的双特异性抗体中是独一无二的，因为它们小而坚固，可以结晶。双抗体是通过肽接头连接重链和轻链的可变区而产生的。由于接头的长度较短，不允许可变区的分子内结合。相反，来自不同肽链的可变区结合在一起，形成具有两个抗原结合位点的二聚体复合物。先前对双体的晶体学研究表明双体具有非凡的结构多样性。他们还表明，由于 Fv 界面的不稳定性，双抗体中两个 Fv 域的相对取向和相互作用具有很大的灵活性。引入位点特异性突变和二硫键会降低灵活性，从而增加双抗体结构的刚性和可预测性。这些稳定的双抗体将有助于未来应用于结构生物学和蛋白质纳米技术。