5xjf
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal structure of fucosylated IgG Fc Y296W mutant complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa== |
| + | <StructureSection load='5xjf' size='340' side='right' caption='[[5xjf]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5xjf]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XJF FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5xje|5xje]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjf OCA], [http://pdbe.org/5xjf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xjf RCSB], [http://www.ebi.ac.uk/pdbsum/5xjf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/FCG3A_HUMAN FCG3A_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23006327</ref> <ref>PMID:8608639</ref> <ref>PMID:8609432</ref> <ref>PMID:8874200</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/IGG1_HUMAN IGG1_HUMAN]] Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</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 == | ||
| + | Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction between the Fc region of immunoglobulin G1 (IgG1) and Fcgamma receptor IIIa (FcgammaRIIIa), depending on N-glycosylation of these glycoproteins. In particular, core fucosylation of IgG1-Fc N-glycans negatively affects this interaction and thereby compromises ADCC activity. To address the mechanisms of this effect, we performed replica-exchange molecular dynamics simulations based on crystallographic analysis of a soluble form of FcgammaRIIIa (sFcgammaRIIIa) in complex with IgG1-Fc. Our simulation highlights increased conformational fluctuation of the N-glycan at Asn162 of sFcgammaRIIIa upon fucosylation of IgG1-Fc, consistent with crystallographic data giving no interpretable electron density for this N-glycan, except for the innermost part. The fucose residue disrupts optimum intermolecular carbohydrate-carbohydrate interactions, rendering this sFcgammaRIIIa glycan distal from the Fc glycan. Moreover, our simulation demonstrates that core fucosylation of IgG1-Fc affects conformational dynamics and rearrangements of surrounding amino acid residues, typified by Tyr296 of IgG1-Fc, which was more extensively involved in the interaction with sFcgammaRIIIa without Fc core fucosylation. Our findings offer a structural foundation for designing and developing therapeutic antibodies with improved ADCC activity. | ||
| - | + | Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc region on its interaction with Fcgamma receptor IIIa.,Sakae Y, Satoh T, Yagi H, Yanaka S, Yamaguchi T, Isoda Y, Iida S, Okamoto Y, Kato K Sci Rep. 2017 Oct 23;7(1):13780. doi: 10.1038/s41598-017-13845-8. PMID:29062024<ref>PMID:29062024</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5xjf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Iida, S]] | ||
| + | [[Category: Isoda, Y]] | ||
| + | [[Category: Kato, K]] | ||
| + | [[Category: Okamoto, Y]] | ||
| + | [[Category: Sakae, Y]] | ||
| + | [[Category: Satoh, T]] | ||
| + | [[Category: Yagi, H]] | ||
| + | [[Category: Yamaguchi, T]] | ||
| + | [[Category: Yanaka, S]] | ||
| + | [[Category: Cd16]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Fc fragment]] | ||
| + | [[Category: Gamma]] | ||
| + | [[Category: Igg]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Receptor]] | ||
Revision as of 06:04, 1 November 2017
Crystal structure of fucosylated IgG Fc Y296W mutant complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa
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Categories: Iida, S | Isoda, Y | Kato, K | Okamoto, Y | Sakae, Y | Satoh, T | Yagi, H | Yamaguchi, T | Yanaka, S | Cd16 | Complex | Fc fragment | Gamma | Igg | Immune system | Receptor
