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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.
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