A model for the formation and interconversion of protein A-immunoglobulin G soluble complexes.
A model for the formation and interconversion of protein A-immunoglobulin G soluble complexes.
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DOI：
10.4049/jimmunol.132.3.1397
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发表时间：
1984-03
影响因子：
4.4
通讯作者：
D. C. Hanson;V. Schumaker
中科院分区：
文献类型：
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作者：
D. C. Hanson;V. Schumaker
我们提出了葡萄球菌蛋白a （SpA）与兔免疫球蛋白G （IgG）抗体反应形成的可溶性复合物的形成和相互转化模型。该模型的基本元素是根据这些复合物的流体动力学和电子显微镜研究（见随附的论文），以及IgG和SpA的结构和结合特性而建立的。该模型包括IgG- spa结合的特定对称性和结合要求，以及相邻IgG分子之间的空间约束。我们讨论了这种约束如何影响平衡配合物的组装和分布。在制定了一个方便的符号表示IgG-SpA配合物后，建议的模型被用来构建合理的结构，为适度过量的SpA观察到的四种主要配合物。这些稳定配合物在不同IgG:SpA比例下的分布，以及LeChatelier原理和简单的热力学推导，被用来预测平衡结构的可能排列。此外，根据报道的x射线衍射和氨基酸序列数据，构建了IgG过量形成的独特IgG4-SpA2复合物的比例模型。用一个直观的热力学论证表明，所建议的空间约束可能导致4个7到15S配合物向独特的17S配合物的空前可逆转变。计算机模拟被用来预测在不同的IgG:SpA比率下各种提出的配合物的平衡浓度。为了支持所建议的结构，计算的热力学分布与用超离心机测量的结果惊人地吻合。我们指出了这些配合物，特别是17S配合物的排列方式，可以解释它们的许多新特性，如抗原诱导的构象变化。不同种类的抗体形成的SpA复合物在补体活化和沉淀形成方面的差异也讨论了复合物结构安排的可能差异。
We present a model for the formation and interconversion of the soluble complexes formed by reacting staphylococcal protein A (SpA) with rabbit immunoglobulin G (IgG) antibodies. The basic elements of the model are developed from reported hydrodynamic and electron microscopic studies of these complexes (see accompanying companion paper), together with established structural and binding properties of IgG and SpA. The model includes specific symmetry and binding requirements for IgG-SpA combination, and a steric constraint between neighboring IgG molecules. We discuss how such a constraint could influence the assembly and distribution of equilibrium complexes. After formulating a convenient symbolism for representing IgG-SpA complexes, the suggested model is used to construct plausible structures for the four predominant complexes observed in moderate SpA excess. Distributions of these stable complexes at different IgG:SpA ratios, together with LeChatelier's principle and a straightforward thermodynamic derivation, are used to predict likely arrangements of equilibrium structures. Also, a scale model of the unique IgG4-SpA2 complex formed in IgG excess is constructed from reported x-ray diffraction and amino acid sequence data. An intuitive thermodynamic argument is used to show that the suggested steric constraint could cause the rather unprecedented reversible transformation of the four 7 to 15S complexes into the unique 17S complex. A computer simulation is used to predict equilibrium concentrations of the various proposed complexes at different IgG:SpA ratios. In support of the suggested structures, the calculated thermodynamic distributions agree surprisingly well with those measured with the ultracentrifuge. We point out how the proposed arrangements of the complexes, and in particular the 17S complex, can account for many of their novel properties, such as antigen-induced conformational changes. Reported differences in complement activation and precipitate formation by SpA complexes formed with antibodies from various species are also discussed with regard to possible differences in structural arrangements of the complexes.