Abstract
PROTEIN G is a cell-surface protein from Streptococcus1,2 which binds to IgG molecules from a wide range of species with an affinity comparable to that of antigen3,4. 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 β-strand in the protein G domain forms an antiparallel interaction with the last β-strand in the constant heavy chain domain of the immunoglobulin, thus extending the β-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.
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Derrick, J., Wigley, D. Crystal structure of a streptococcal protein G domain bound to an Fab fragment. Nature 359, 752–754 (1992). https://doi.org/10.1038/359752a0
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DOI: https://doi.org/10.1038/359752a0
