Interaction between the antigen and antibody is controlled by the constant domains: Normal mode dynamics of the HEL-HyHEL-10 complex
Interaction between the antigen and antibody is controlled by the constant domains: Normal mode dynamics of the HEL-HyHEL-10 complex
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DOI：
10.1110/ps.03100803
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发表时间：
2003-10-01
期刊：
影响因子：
8
通讯作者：
Umeyama, H
中科院分区：
文献类型：
--
作者：
Adachi, M;Kurihara, Y;Umeyama, H
单克隆抗体（HyHEL- 10）的抗原结合片段（Fab）由可变结构域（Fv）和恒定结构域（CL-CH 1）组成。计算了鸡蛋溶菌酶（HEL）与Fab、HEL与Fv等复合物的三维结构，发现HEL-Fab和HEL-Fv复合物之间只有很小的结构变化。然而，HEL-Fv具有比HEL-Fab低一个数量级的解离常数。计算结果表明，HEL-Fab的Cot涨落与HEL-Fv不同，其动力学与蛋白质相互作用有关。CL-CH 1不仅可以在CL-CH 1和Fv之间的局部界面周围产生影响，而且可以在HEL和Fv之间的相互作用区域周围产生影响，所述相互作用区域在纵向上远离。在HEL-Fv中发现了18个水分子，而在HEL-Fab中发现了1个水分子。这些溶剂分子可能占据空穴和通道，这可能由于复合物的不完全互补而发生。因此，可以认为Fv和HEL之间的界面周围的原子振动的抑制与通过完全去溶剂化形成有利且致密的界面有关。这表明通过修饰CL-CH 1获得控制抗原-抗体亲和力的能力。轻链恒定区的第二上环（UL 2-CL）是几种轻链中保守的基因，其波动变化最显著。UL 2-CL在蛋白质工程中具有重要的应用价值，是一种具有潜在应用前景的蛋白质工程修饰剂。
The antigen binding fragment (Fab) of a monoclonal antibody (HyHEL- 10) consists of variable domains (Fv) and constant domains (CL-CH1). Normal modes have been calculated from the three-dimensional structures of hen egg lysozyme (HEL) with Fab, those of HEL with Fv, and so on. Only a small structural change was found between HEL-Fab and HEL-Fv complexes. However, HEL-Fv had a one order of magnitude lower dissociation constant than HEL-Fab. The Cot fluctuations of HEL-Fab differed from those of HEL-Fv with normal mode calculation, and the dynamics can be thought to be related to the protein-protein interactions. CL-CH1 may have influence not only around local interfaces between CL-CH1 and Fv, but also around the interacting regions between HEL and Fv, which are longitudinally distant. Eighteen water molecules were found in HEL-Fv around the interface between HEL and Fv compared with one water molecule in HEL-Fab. These solvent molecules may occupy the holes and channels, which may occur due to imperfect complementarity of the complex. Therefore, the suppression of atomic vibration around the interface between Fv and HEL can be thought to be related to favorable and compact interface formation by complete desolvation. It is suggested that the ability to control the antigen-anti body affinity is obtained from modifying the CL-CH1. The second upper loop in the constant domain of the light chain (UL2-CL), which is a conserved gene in several light chains, showed the most remarkable fluctuation changes. UL2-CL could play an important role and could be attractive for modification in protein engineering.