Nanobodies (Nbs) are a class of antigen-binding protein derived from camelid immune systems, which achieve equivalent binding affinities and specificities to classical antibodies (Abs) despite being comprised of only a single variable domain. Here, we use a data set of 156 unique Nb:antigen complex structures to characterize Nb-antigen binding and draw comparison to a set of 156 unique Ab:antigen structures. We analyse residue composition and interactions at the antigen interface, together with structural features of the paratopes of both data sets. Our analysis finds that the set of Nb structures displays much greater paratope diversity, in terms of the structural segments involved in the paratope, the residues used at these positions to contact the antigen and furthermore the type of contacts made with the antigen. Our findings suggest a different relationship between contact propensity and sequence variability from that observed for Ab VH domains. The distinction between sequence positions that control interaction specificity and those that form the domain scaffold is much less clear-cut for Nbs, and furthermore H3 loop positions play a much more dominant role in determining interaction specificity.

中文翻译：

---

纳米抗体互补位的分析揭示了比经典抗体更大的多样性。


纳米抗体 (Nbs) 是一类源自骆驼科动物免疫系统的抗原结合蛋白，尽管仅由单个可变结构域组成，但它仍具有与经典抗体 (Abs) 相当的结合亲和力和特异性。在这里，我们使用 156 个独特的 Nb：抗原复合物结构的数据集来表征 Nb-抗原结合，并与一组 156 个独特的 Ab：抗原结构进行比较。我们分析了抗原界面处的残基组成和相互作用，以及两个数据集互补位的结构特征。我们的分析发现，就互补位所涉及的结构片段、这些位置处用于接触抗原的残基以及与抗原的接触类型而言，Nb 结构集显示出更大的互补位多样性。我们的研究结果表明，接触倾向和序列变异之间的关系与 Ab VH 结构域观察到的关系不同。对于 Nbs 来说，控制相互作用特异性的序列位置和形成结构域支架的序列位置之间的区别不太明确，而且 H3 环位置在确定相互作用特异性方面发挥着更重要的作用。