3RY4

1.5 Angstrom resolution structure of glycosylated fcgammariia (low-responder polymorphism)

Summary for 3RY4

• Entry DOI: 10.2210/pdb3ry4/pdb
• Related: 3RY5 3RY6
• Descriptor: Low affinity immunoglobulin gamma Fc region receptor II-a, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total)
• Functional Keywords: fc receptor, cd32, immunoglobulin superfamily, low responder polymorphism, cell membrane, glycoprotein, igg-binding protein, immunoglobulin domain, membrane, phosphoprotein, receptor, transmembrane, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 19500.75

Authors

Ramsland, P.A.,Farrugia, W.,Hogarth, P.M. (deposition date: 2011-05-11, release date: 2011-08-31, Last modification date: 2024-11-06)

Primary citation

Ramsland, P.A.,Farrugia, W.,Bradford, T.M.,Sardjono, C.T.,Esparon, S.,Trist, H.M.,Powell, M.S.,Tan, P.S.,Cendron, A.C.,Wines, B.D.,Scott, A.M.,Hogarth, P.M.
Structural Basis for Fc{gamma}RIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes.
J.Immunol., 187:3208-3217, 2011

PubMed Abstract: The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. FcγRIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of FcγRIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of FcγRIIa (FcγRIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence FcγRIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for FcγRIIa (IV.3), FcγRIIb (X63-21), and a pan FcγRII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of FcγRIIa and FcγRIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of FcγRIIa-HR binds Ag-Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly.

PubMed: 21856937
DOI: 10.4049/jimmunol.1101467

Experimental method

X-RAY DIFFRACTION (1.5 Å)