Derrick J P, Wigley D B
Department of Biochemistry, University of Leicester, UK.
Nature. 1992 Oct 22;359(6397):752-4. doi: 10.1038/359752a0.
Protein G is a cell-surface protein from Streptococcus which binds to IgG molecules from a wide range of species with an affinity comparable to that of antigen. The high affinity of protein G for the Fab portion of IgG poses a particular challenge in molecular recognition, given the variability of heavy chain subclass, light chain type and complementarity-determining regions. Here we report the crystal structure of a complex between a protein G domain and an immunoglobulin Fab fragment. An outer beta-strand in the protein G domain forms an antiparallel interaction with the last beta-strand in the constant heavy chain domain of the immunoglobulin, thus extending the beta-sheet into the protein G. The interaction between secondary structural elements in Fab and protein G provides an ingenious solution to the problem of maintaining a high affinity for many different IgG molecules. The structure also contrasts with Fab-antigen complexes, in which all contacts with antigen are mediated by the variable regions of the antibody, and to our knowledge provides the first details of interaction of the constant regions of Fab with another protein.
蛋白G是一种来自链球菌的细胞表面蛋白，它能与多种物种的IgG分子结合，亲和力与抗原相当。鉴于重链亚类、轻链类型和互补决定区的变异性，蛋白G对IgG的Fab部分的高亲和力在分子识别中构成了特殊挑战。在此，我们报道了蛋白G结构域与免疫球蛋白Fab片段复合物的晶体结构。蛋白G结构域中的一条外部β链与免疫球蛋白恒定重链结构域中的最后一条β链形成反平行相互作用，从而将β折叠延伸至蛋白G中。Fab和蛋白G中二级结构元件之间的相互作用为维持对许多不同IgG分子的高亲和力问题提供了巧妙的解决方案。该结构也与Fab-抗原复合物形成对比，在Fab-抗原复合物中，与抗原的所有接触均由抗体的可变区介导，据我们所知，该结构首次提供了Fab恒定区与另一种蛋白相互作用的详细信息。
