Novel arrangement of immunoglobulin variable domains: X-ray crystallographic analysis of the lambda-chain dimer Bence-Jones protein Loc.
Novel arrangement of immunoglobulin variable domains: X-ray crystallographic analysis of the lambda-chain dimer Bence-Jones protein Loc.
复制标题
免疫球蛋白可变域的新排列：lambda 链二聚体 Bence-Jones 蛋白 Loc 的 X 射线晶体学分析。
DOI：
10.1021/bi00339a025
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发表时间：
1985
期刊：
影响因子：
2.9
通讯作者：
Schiffer,M
中科院分区：
文献类型：
--
作者：
Chang,CH;Short,MT;Westholm,FA;Stevens,FJ;Wang,BC;FureyJr,W;Solomon,A;Schiffer,M
我们鉴定并结晶了一种人XI轻链二聚体Bence-Jones Protein Loc，它具有CXI基因Meg的可变(V)区抗原决定簇和恒定(C)区决定簇。晶体结构测定为3-A分辨率，R因子为0.27。V和C结构域的两个轴形成的角度是97，这是迄今为止发现的抗体片段中最小的。Loc轻链的两个V结构域形成的抗原结合部位与其他免疫球蛋白分子(轻链二聚体和Fab片段)形成的抗原结合部位有很大的不同，这是可以获得X射线结晶学数据的。然而，在其他抗体片段中，V结构域通过一个局部双轴联系在一起，而在蛋白质Loc中，一个平移分量为3.5°的局部双螺旋轴将V结构域联系在一起。与先前表征的抗体结构中由V结构域相互作用形成的经典抗原结合“口袋”不同，蛋白质Loc中的V区域结合导致结合部位的中心突出，在突出的两侧有凹槽。蛋白Loc的结构表明，免疫球蛋白在物理上能够形成比迄今所见的更多样化的抗原结合部位谱。此外，结合部位的不同寻常的突出性质可能类似于一些抗独特型抗体所需的结构。此外，决定互补的残基形成两个独立凹槽的一部分。因此，Loc结构可能被视为T细胞受体的一种可能模型，它由两个轻链样多肽组成，可以同时结合两种不同的蛋白质。
We have characterized andcrystallized a human XI light-chain dimer, Bence-Jones protein Loc, which has variable (V) region antigenic determinants characteristic for the XI subgroup and constant (C) region determinants of the CXI gene Meg. The crystal structure was determined to 3-A resolution; the R factor is 0.27. The angle formed by the twofold axes of the V and C domains, the “elbow bend”, is 97, the smallest found so far for an antibody fragment. The antigen-binding site formed by the two V domains of the Loc light chain differs significantly from those of other immunoglobulin molecules (light-chain dimers and Fab fragments) for which X-ray crystallographic data are available. Whereas, in other antibody fragments, the V domains are related by a local twofold axis, a local twofold screw axis with a translational component of 3.5 Á relates the V domains in protein Loc. In contrast to the classic antigen binding “pocket” formed by V domain interactions inthe previously characterized antibody structures, the V region associations in protein Loc result in a central protrusion in the binding site, with grooves on two sides of the protrusion. The structure of protein Loc indicates that immunoglobulins are physically capable of forming a more diverse spectrum of antigen-binding sites than has been heretofore apparent. Moreover, the unusual protruding nature of the binding site may be analogous to structures required for some anti-idiotypic antibodies. Further, the complementarity-determining residues form parts of two independent grooves. Therefore, the Loc structure might be viewed as a possible model for the T-cell receptor, which is composed of two light-chain-like polypeptides and can simultaneously bind two different proteins.