Crystallographic structure of an intact IgG1 monoclonal antibody
Crystallographic structure of an intact IgG1 monoclonal antibody
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DOI：
10.1006/jmbi.1997.1508
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发表时间：
1998-02-06
影响因子：
5.6
通讯作者：
McPherson, A
中科院分区：
文献类型：
--
作者：
Harris, LJ;Skaletsky, E;McPherson, A
苯巴比妥（IgG 1亚类）的完整单克隆抗体的结构已通过X射线晶体学确定为3.2埃分辨率。该分子在单斜晶胞中可视化，该单斜晶胞具有作为不对称单位的完整免疫球蛋白。两个Fab片段，均具有155度的肘角，通过179.7度的旋转加上沿沿着9埃的近似二分体的平移而相关。这是在结构确定的抗体中首次观察到这种Fab翻译。Fc的约2倍独立于相关Fab，与Fab二联体成107度角。Fab的长轴之间的角度为115度，这是迄今观察到的最锐角，产生扭曲的Y形分子。这与完整结构已知的唯一其他完整IgG（2a）的扭曲T形形成对比。初级晶格相互作用通过V-H反平行β带的形成而产生，β带的链由与H2相关的伪二分体和来自相邻分子的L3高变环贡献。虽然一个C（H）2结构域是移动的，但Fab和Fc的三个结构域是明确定义的，连接Fab与Fc的铰链多肽以及共价连接的寡糖也是如此。在铰链多肽、一个C（H）2结构域的糖基化环和寡糖之间观察到直接相互作用。晶格相互作用显然影响，甚至可能决定在该晶体中观察到的抗体的整体构象。与先前确定的完整抗体结构的IgG 1的比较，扩展了由片段灵活性引起的构象范围。(C)出版社：Academic Press Limited。
The structure of an intact monoclonal antibody for phenobarbital, subclass IgG1, has been determined to 3.2 Angstrom resolution by X-ray crystallography The molecule was visualized in a monoclinic unit cell having an entire immunoglobulin as the asymmetric unit. The two Fab segments, both with elbow angles of 155 degrees, were related by a rotation of 179.7 degrees plus a translation along the approximate dyad of 9 Angstrom. This is the first observation of such an Fab translation in a structurally defined antibody. The approximate 2-fold of the Fc was independent of that relating Fabs, making an angle of 107 degrees with the Fab dyad. The angle between long axes of the Fabs was 115 degrees, the most acute angle yet observed, yielding a distorted Y shaped molecule. This is in contrast to the distorted T shape of the only other intact IgG (2a) whose complete structure is known. Primary lattice interactions arise through formation of V-H antiparallel beta ribbons whose strands are contributed by pseudo dyad related H2, and by L3 hypervariable loops from neighboring molecules. While one C(H)2 domain was mobile, Fabs and three domains of the Fc were well defined, as were hinge polypeptides connecting Fabs to the Fc, and the covalently attached oligosaccharides. Direct interactions are observed between hinge polypeptides, the glycosylated loop of one C(H)2 domain, and the oligosaccharide. Lattice interactions clearly influence, perhaps even determine the overall conformation of the antibody observed in this crystal. Comparison of this IgG1 with previously determined intact antibody structures extends the conformational range arising from segmental flexibility. (C) 1998 Academic Press Limited.