Recognition of immunoglobulins by Fcgamma receptors.
Fc receptors mediate antibody dependent inflammatory response and cytotoxicity as well as certain autoimmune dysfunctions. Fcgamma receptors interact with IgG antibodies by binding the Fc portion of the antibody in asymmetric fashion creating a 1:1 receptor-ligand stoichiometry. Regions of the C-terminal domain of Fc receptors including the BC, C'E, FG loops, and the C' beta-strand interact with immunoglobulins. The lower hinge region of the antibody contributes most of the binding to the low affinity Fcgamma receptors. Carbohydrates attached to the conserved glycosylation site on Fc portion of an antibody are critical to the recognition of immunoglobulins by the low affinity Fcgamma receptor. They are likely to function as a substitution for the hydrophobic core to preserve an optimal lower hinge conformation for the receptor binding. Subtype specificities of FcgammaRIII receptor probably are determined by the length of the lower hinge regions of immunoglobulins, but not their amino acid composition as revealed by the binding study of the lower hinge peptides. These studies also paved a new way for designing of novel therapeutic compounds in fighting autoimmune diseases.
Radaev
Sergei
S
Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Sun
Peter
P
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000737:chemistry* / Q000276:immunology
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007136:Immunoglobulins; D008024:Ligands; D017452:Receptors, IgG