Spinelli S, Tegoni M, Frenken L, van Vliet C, Cambillau C
Architecture et Fonction des Macromolécules Biologiques, CNRS and Universités d'Aix-Marseille I and II, 31 Chemin Joseph Aiguier, Marseille Cedex 20, UMR-6098, 13402, France.
J Mol Biol. 2001 Aug 3;311(1):123-9. doi: 10.1006/jmbi.2001.4856.
Camelids, camels and llamas, have a unique immune system able to produce heavy-chain only antibodies. Their VH domains (VHHs) are the smallest binding units produced by immune systems, and therefore suitable for biotechnological applications through heterologous expression. The recognition of protein antigens by these VHHs is rather well documented, while less is known about the VHH/hapten interactions. The recently reported X-ray structure of a VHH in complex with a copper-containing azo-dye settled the ability of VHH to recognize haptens by forming a cavity between the three complementarity-determining regions (CDR). Here we report the structures of a VHH (VHH A52) free or complexed with an azo-dye, RR1, without metal ion. The structure of the complex illustrates the involvement of CDR2, CDR3 and a framework residue in a lateral interaction with the hapten. Such a lateral combining site is comparable to that found in classical antibodies, although in the absence of the VL.
骆驼科动物，如骆驼和美洲驼，拥有独特的免疫系统，能够产生仅含重链的抗体。它们的重链可变区（VHHs）是免疫系统产生的最小结合单元，因此适合通过异源表达用于生物技术应用。这些VHHs对蛋白质抗原的识别已有相当多的文献记载，而关于VHH/半抗原相互作用的了解则较少。最近报道的一个与含铜偶氮染料复合的VHH的X射线结构确定了VHH通过在三个互补决定区（CDR）之间形成一个腔来识别半抗原的能力。在这里，我们报道了一个游离的或与无金属离子的偶氮染料RR1复合的VHH（VHH A52）的结构。复合物的结构表明CDR2、CDR3和一个骨架残基参与了与半抗原的侧向相互作用。这样一个侧向结合位点与经典抗体中的类似，尽管没有轻链可变区（VL）。
