Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Gent, Belgium.
Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Gent, Belgium.
Biotechnol Adv. 2023 May-Jun;64:108120. doi: 10.1016/j.biotechadv.2023.108120. Epub 2023 Feb 9.
In contrast to other species, cattle possess exceptional antibodies with ultra-long complementarity-determining regions (ulCDRs) that can consist of 40-70 amino acids. The bovine ulCDR is folded into a stalk and a disulfide-rich knob domain. The binding to the antigen is via the 3-6 kDa knob. There exists an immense sequence and structural diversity in the knob that enables binding to different antigens. Here we summarize the current knowledge of the ulCDR structure and provide an overview of the approaches to discover ulCDRs against novel antigens. Furthermore, we outline protein engineering approaches inspired by the natural ulCDRs. Finally, we discuss the enormous potential of using isolated bovine knobs, also named picobodies, as the smallest antigen-binding domains derived from natural antibodies.
与其他物种相比，牛具有独特的抗体，其超长互补决定区（ulCDR）可由 40-70 个氨基酸组成。牛的 ulCDR 折叠成一个柄和一个富含二硫键的 knob 结构域。通过 3-6 kDa 的 knob 与抗原结合。knob 存在巨大的序列和结构多样性，使其能够与不同的抗原结合。在这里，我们总结了 ulCDR 结构的最新知识，并概述了发现针对新型抗原的 ulCDR 的方法。此外，我们还概述了受天然 ulCDR 启发的蛋白质工程方法。最后，我们讨论了使用分离的牛 knob（也称为 picobodies）作为源自天然抗体的最小抗原结合结构域的巨大潜力。
