title: Crystal structure of a streptococcal protein G domain bound to an Fab fragment.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Leicester, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Derrick
authors.forename: D B
authors.initials: DB
authors.lastname: Wigley
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000648:ultrastructure*; D003461:Crystallography; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000648:ultrastructure*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013291:Streptococcus / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D007140:Immunoglobulin Fab Fragments; D046911:Macromolecular Substances