3ay4
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of nonfucosylated Fc complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa== | |
| - | + | <StructureSection load='3ay4' size='340' side='right' caption='[[3ay4]], [[Resolution|resolution]] 2.20Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3ay4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AY4 FirstGlance]. <br> | |
| - | ==Disease== | + | </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=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">[[2dts|2dts]], [[3ave|3ave]], [[1e4k|1e4k]], [[1t83|1t83]], [[1t89|1t89]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), FCGR3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3ay4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ay4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ay4 RCSB], [http://www.ebi.ac.uk/pdbsum/3ay4 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[http://omim.org/entry/254500 254500]]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4. | [[http://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[http://omim.org/entry/254500 254500]]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4. | ||
| + | == Function == | ||
| + | |||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Removal of the fucose residue from the N-glycans of the Fc portion of immunoglobulin G (IgG) results in a dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) through improved affinity for Fcgamma receptor IIIa (FcgammaRIIIa). Here, we present the 2.2-A structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of FcgammaRIIIa (sFcgammaRIIIa) with two N-glycosylation sites. The crystal structure shows that one of the two N-glycans of sFcgammaRIIIa mediates the interaction with nonfucosylated Fc, thereby stabilizing the complex. However, fucosylation of the Fc N-glycans inhibits this interaction, because of steric hindrance, and furthermore, negatively affects the dynamics of the receptor binding site. Our results offer a structural basis for improvement in ADCC of therapeutic antibodies by defucosylation. | ||
| - | + | Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans.,Mizushima T, Yagi H, Takemoto E, Shibata-Koyama M, Isoda Y, Iida S, Masuda K, Satoh M, Kato K Genes Cells. 2011 Nov;16(11):1071-1080. doi:, 10.1111/j.1365-2443.2011.01552.x. PMID:22023369<ref>PMID:22023369</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Iida, S | + | [[Category: Iida, S]] |
| - | [[Category: Isoda, Y | + | [[Category: Isoda, Y]] |
| - | [[Category: Kato, K | + | [[Category: Kato, K]] |
| - | [[Category: Mizushima, T | + | [[Category: Mizushima, T]] |
| - | [[Category: Satoh, M | + | [[Category: Satoh, M]] |
| - | [[Category: Shibata-Koyama, M | + | [[Category: Shibata-Koyama, M]] |
| - | [[Category: Takemoto, E | + | [[Category: Takemoto, E]] |
| - | [[Category: Yagi, H | + | [[Category: Yagi, H]] |
[[Category: Cd16]] | [[Category: Cd16]] | ||
[[Category: Complex]] | [[Category: Complex]] | ||
Revision as of 13:53, 18 December 2014
Crystal structure of nonfucosylated Fc complexed with bis-glycosylated soluble form of Fc gamma receptor IIIa
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Categories: Homo sapiens | Iida, S | Isoda, Y | Kato, K | Mizushima, T | Satoh, M | Shibata-Koyama, M | Takemoto, E | Yagi, H | Cd16 | Complex | Fc fragment | Gamma | Igg | Immune system | Receptor
