5w5m
From Proteopedia
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==Crystal structure of human IgG4-Sigma1 Fc fragment== | ==Crystal structure of human IgG4-Sigma1 Fc fragment== | ||
| - | <StructureSection load='5w5m' size='340' side='right' caption='[[5w5m]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5w5m' size='340' side='right'caption='[[5w5m]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5w5m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W5M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W5M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w5m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W5M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W5M FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5w5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w5m OCA], [http://pdbe.org/5w5m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w5m RCSB], [http://www.ebi.ac.uk/pdbsum/5w5m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w5m ProSAT]</span></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=5w5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w5m OCA], [http://pdbe.org/5w5m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w5m RCSB], [http://www.ebi.ac.uk/pdbsum/5w5m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w5m ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcgamma) receptor-expressing immune cells. We previously reported on a human IgG2 variant termed IgG2sigma with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and Fcgamma receptor binding assays. Here, we extend that work to IgG1 and IgG4 antibodies, alternative subtypes which may offer advantages over IgG2 antibodies. In several in vitro and in vivo assays, the IgG1sigma and IgG4sigma variants showed equal or even lower Fc-related activities than the corresponding IgG2sigma variant. In particular, IgG1sigma and IgG4sigma variants demonstrate complete lack of effector function as measured by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and in vivo T-cell activation. The IgG1sigma and IgG4sigma variants showed acceptable solubility and stability, and typical human IgG1 pharmacokinetic profiles in human FcRn-transgenic mice and cynomolgus monkeys. In silico T-cell epitope analyses predict a lack of immunogenicity in humans. Finally, crystal structures and simulations of the IgG1sigma and IgG4sigma Fc domains can explain the lack of Fc-mediated immune functions. These variants show promise for use in those therapeutic antibodies and Fc fusions for which the Fc domain should be immunologically "silent". | ||
| + | |||
| + | Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality.,Tam SH, McCarthy SG, Armstrong AA, Somani S, Wu SJ, Liu X, Gervais A, Ernst R, Saro D, Decker R, Luo J, Gilliland GL, Chiu ML, Scallon BJ Antibodies (Basel). 2017 Sep 1;6(3). pii: antib6030012. doi:, 10.3390/antib6030012. PMID:31548527<ref>PMID:31548527</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5w5m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Armstrong, A A]] | [[Category: Armstrong, A A]] | ||
[[Category: Gilliland, G L]] | [[Category: Gilliland, G L]] | ||
Revision as of 11:25, 13 November 2019
Crystal structure of human IgG4-Sigma1 Fc fragment
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