Chothia C, Novotný J, Bruccoleri R, Karplus M
J Mol Biol. 1985 Dec 5;186(3):651-63. doi: 10.1016/0022-2836(85)90137-8.
We have analyzed the structure of the interface between VL and VH domains in three immunoglobulin fragments: Fab KOL, Fab NEW and Fab MCPC 603. About 1800 A2 of protein surface is buried between the domains. Approximately three quarters of this interface is formed by the packing of the VL and VH beta-sheets in the conserved "framework" and one quarter from contacts between the hypervariable regions. The beta-sheets that form the interface have edge strands that are strongly twisted (coiled) by beta-bulges. As a result, the edge strands fold back over their own beta-sheet at two diagonally opposite corners. When the VL and VH domains pack together, residues from these edge strands form the central part of the interface and give what we call a three-layer packing; i.e. there is a third layer composed of side-chains inserted between the two backbone side-chain layers that are usually in contact. This three-layer packing is different from previously described beta-sheet packings. The 12 residues that form the central part of the three observed VL-VH packings are absolutely or very strongly conserved in all immunoglobulin sequences. This strongly suggests that the structure described here is a general model for the association of VL and VH domains and that the three-layer packing plays a central role in forming the antibody combining site.
我们分析了三种免疫球蛋白片段（Fab KOL、Fab NEW和Fab MCPC 603）中VL和VH结构域之间的界面结构。结构域之间掩埋了约1800 Ų的蛋白质表面。该界面大约四分之三由保守“框架”中VL和VHβ折叠片层的堆积形成，四分之一由高变区之间的接触形成。形成界面的β折叠片层具有被β凸起强烈扭曲（盘绕）的边缘链。结果，边缘链在两个对角相对的角处折回到其自身的β折叠片层上。当VL和VH结构域堆积在一起时，这些边缘链的残基形成界面的中心部分，并形成我们所说的三层堆积；即存在由插入通常相互接触的两个主链侧链层之间的侧链组成的第三层。这种三层堆积不同于先前描述的β折叠片层堆积。在所有免疫球蛋白序列中，形成观察到的三种VL-VH堆积中心部分的12个残基绝对或非常保守。这强烈表明这里描述的结构是VL和VH结构域缔合的通用模型，并且三层堆积在形成抗体结合位点中起核心作用。
