3ry4
1.5 Angstrom resolution structure of glycosylated fcgammariia (low-responder polymorphism)
Structural highlights
FunctionFCG2A_HUMAN Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens.[1] Publication Abstract from PubMedThe 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. FcgammaRIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of FcgammaRIIa (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 FcgammaRIIa (FcgammaRIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence FcgammaRIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for FcgammaRIIa (IV.3), FcgammaRIIb (X63-21), and a pan FcgammaRII 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 FcgammaRIIa and FcgammaRIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of FcgammaRIIa-HR binds Ag-Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly. Structural Basis for Fc{gamma}RIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes.,Ramsland PA, Farrugia W, Bradford TM, Sardjono CT, Esparon S, Trist HM, Powell MS, Tan PS, Cendron AC, Wines BD, Scott AM, Hogarth PM J Immunol. 2011 Aug 19. PMID:21856937[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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