5d6d
From Proteopedia
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==Crystal structure of GASDALIE IgG1 Fc in complex with FcgRIIIa== | ==Crystal structure of GASDALIE IgG1 Fc in complex with FcgRIIIa== | ||
<StructureSection load='5d6d' size='340' side='right' caption='[[5d6d]], [[Resolution|resolution]] 3.13Å' scene=''> | <StructureSection load='5d6d' size='340' side='right' caption='[[5d6d]], [[Resolution|resolution]] 3.13Å' scene=''> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FCG3A_HUMAN FCG3A_HUMAN]] Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.<ref>PMID:21768335</ref> <ref>PMID:22023369</ref> | [[http://www.uniprot.org/uniprot/FCG3A_HUMAN FCG3A_HUMAN]] Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.<ref>PMID:21768335</ref> <ref>PMID:22023369</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Fc region of Immunoglobulin G (IgG) initiates inflammatory responses such as antibody-dependent cell-mediated cytotoxicity (ADCC) through binding to activating Fc receptors (FcgammaRI, FcgammaRIIa, FcgammaRIIIa). These receptors are expressed on the surface of immune cells including macrophages, dendritic cells, and natural killer cells. An inhibitory receptor, FcgammaRIIb, is expressed on macrophages and other myeloid leukocytes simultaneously with the activating receptor FcgammaRIIa, thereby setting a threshold for cell activation. The affinity of IgG Fc for binding activating Fc receptors depends on IgG subclass and the composition of N-linked glycans attached to a conserved asparagine in the Fc CH2 domain. For example, Fc regions with afucosylated glycans bind more tightly to FcgammaRIIIa than fucosylated Fc, and afucosylated Fcs exhibit enhanced ADCC activity in vivo and in vitro. Enhanced pro-inflammatory responses have also been seen for Fc regions with amino acid substitutions. GASDALIE Fc is an Fc mutant (G236A/S239D/A330L/I332E) that exhibits a higher affinity for FcgammaRIIIa and increased effector functions in vivo compared to wild-type Fc. To explore its altered functions, we compared the affinities of GASDALIE and wild-type Fc for activating and inhibitory FcgammaRs. We also determined the crystal structure of GASDALIE Fc alone and bound to FcgammaRIIIa. The overall structure of GASDALIE Fc alone was similar to wild-type Fc structures, however, increased electrostatic interactions in the GASDALIE Fc:FcgammaRIIIa interface compared with other Fc:FcgammaR structures suggest a mechanism for the increased affinity of GASDALIE Fc for FcgammaRIIIa. | ||
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| + | Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcgammaRIIIa.,Ahmed AA, Keremane SR, Vielmetter J, Bjorkman PJ J Struct Biol. 2016 Apr;194(1):78-89. doi: 10.1016/j.jsb.2016.02.001. Epub 2016, Feb 2. PMID:26850169<ref>PMID:26850169</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5d6d" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 10:18, 26 February 2016
Crystal structure of GASDALIE IgG1 Fc in complex with FcgRIIIa
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Categories: Ahmed, A A | Bjorkman, P J | Adcc | Igg | Immune system
