Noël Floriane, Malpertuy Alain, de Brevern Alexandre G
INSERM, U 1134, DSIMB, F-75739 Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, UMR_S 1134, F-75739 Paris, France; Institut National de la Transfusion Sanguine (INTS), F-75739 Paris, France; Laboratoire d'Excellence GR-Ex, F-75739 Paris, France.
Atragene, F-94200 Ivry-sur-Seine, France.
Biochimie. 2016 Dec;131:11-19. doi: 10.1016/j.biochi.2016.09.005. Epub 2016 Sep 6.
The VHHs are antigen-binding region/domain of camelid heavy chain antibodies (HCAb). They have many interesting biotechnological and biomedical properties due to their small size, high solubility and stability, and high affinity and specificity for their antigens. HCAb and classical IgGs are evolutionary related and share a common fold. VHHs are composed of regions considered as constant, called the frameworks (FRs) connected by Complementarity Determining Regions (CDRs), a highly variable region that provide interaction with the epitope. Actually, no systematic structural analyses had been performed on VHH structures despite a significant number of structures. This work is the first study to analyse the structural diversity of FRs of VHHs. Using a structural alphabet that allows approximating the local conformation, we show that each of the four FRs do not have a unique structure but exhibit many structural variant patterns. Moreover, no direct simple link between the local conformational change and amino acid composition can be detected. These results indicate that long-range interactions affect the local conformation of FRs and impact the building of structural models.
VHH是骆驼科动物重链抗体（HCAb）的抗原结合区域/结构域。由于其尺寸小、溶解度和稳定性高，以及对其抗原具有高亲和力和特异性，它们具有许多有趣的生物技术和生物医学特性。HCAb与经典IgG在进化上相关且具有共同的折叠结构。VHH由被认为是恒定的区域组成，称为框架区（FRs），由互补决定区（CDRs）连接，互补决定区是一个高度可变的区域，负责与表位相互作用。实际上，尽管已有大量VHH结构，但尚未对其进行系统的结构分析。这项工作是首次分析VHH框架区结构多样性的研究。使用一种能够近似局部构象的结构字母表，我们发现四个框架区中的每一个都没有独特的结构，而是呈现出许多结构变体模式。此外，在局部构象变化和氨基酸组成之间未检测到直接的简单联系。这些结果表明，长程相互作用会影响框架区的局部构象，并影响结构模型的构建。
