Abstract：
The immune systems protect vertebrates from foreign molecules or antigens, and antibodies are important mediators of this system. The sequences and structural features of antibodies vary depending on species. Many of antibodies from vertebrates, including camelids, have both heavy and light chain variable domains, but camelids also have antibodies that lack the light chains. In antibodies that lack light chains, the C-terminal variable region is called the VHH domain. Antibodies recognize antigens through six complementarity-determining regions (CDRs). The third CDR of the heavy chain (CDR-H3) is at the center of the antigen-binding site and is diverse in terms of sequence and structure. Due to the importance of antibodies in basic science as well as in medical applications, there have been many studies of CDR-H3s of antibodies that possess both light and heavy chains. However, nature of CDR-H3s of single-domain VHH antibodies is less well studied. In this chapter, we describe current knowledge of sequence-structure-function correlations of single-domain VHH antibodies with emphasis on CDR-H3. Based on the 370 crystal structures in the Protein Data Bank, we also attempt structural classification of CDR-H3 in single-domain VHH antibodies and discuss lessons learned from the ever-increasing number of the structures.
摘要：
免疫系统保护脊椎动物免受外来分子或抗原的侵害，抗体是这个系统的重要介质。抗体的序列和结构特征根据物种而变化。许多来自脊椎动物的抗体，包括骆驼,具有重链和轻链可变结构域，但是骆驼科动物也有缺乏轻链的抗体。在缺乏轻链的抗体中，C末端可变区称为VHH结构域。抗体通过六个互补决定区(CDR)识别抗原。重链的第三个CDR(CDR-H3)位于抗原结合位点的中心,并且在序列和结构方面是不同的。由于抗体在基础科学和医学应用中的重要性，已经有许多具有轻链和重链的抗体的CDR-H3s的研究。然而,单结构域VHH抗体的CDR-H3s的性质研究较少。在这一章中,我们描述了单结构域VHH抗体的序列-结构-功能相关性的最新知识,重点是CDR-H3.基于蛋白质数据库中的370个晶体结构,我们还尝试了单结构域VHH抗体中CDR-H3的结构分类,并讨论了从结构数量不断增加中获得的经验教训.
