title: Structural basis of the interaction between IgG and Fcgamma receptors.
abstract: The binding of multivalent antigen-antibody complexes to receptors for the Fc portion of IgG (FcgammaR) induces the clustering of the FcgammaR and triggers cell activation leading to defence reactions against pathogens. The Fc portion of IgG consists of two identical polypeptide chains which are related to each other by a 2-fold axis and are folded in two structural domains, the C(H)2 domain, near the flexible hinge region of the IgG molecule, and the C(H)3 domain. We studied the interaction in solution between the Fc fragment of mouse IgG2b and the extracellular region of mouse FcgammaRII. We find that one Fc molecule binds one FcgammaRII molecule only. Using NMR spectroscopy, we show that FcgammaRII binds to a negatively charged area of the C(H)2 domain, corresponding to the lower hinge region, and that the binding of FcgammaRII onto one of the two symmetrically related sites on the Fc induces a conformational change in the other site. We therefore propose a model that explains why IgG molecules are unable to trigger FcgammaR-mediated cellular responses spontaneously in the absence of crosslinking by multivalent antigens.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: C
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: W
authors.initials: W
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Uchiyama
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Enokizono
authors.forename: A
authors.initials: A
authors.lastname: Galinha
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: W H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Y
authors.initials: Y
authors.lastname: Arata
authors.forename: I
authors.initials: I
authors.lastname: Shimada
mesh_terms: D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017452:Receptors, IgG / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D017452:Receptors, IgG