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4c55

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<StructureSection load='4c55' size='340' side='right'caption='[[4c55]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
<StructureSection load='4c55' size='340' side='right'caption='[[4c55]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4c55]] is a 2 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=4C55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C55 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4c55]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C55 FirstGlance]. <br>
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</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=EDO:1,2-ETHANEDIOL'>EDO</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c54|4c54]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c55 OCA], [https://pdbe.org/4c55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c55 RCSB], [https://www.ebi.ac.uk/pdbsum/4c55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c55 ProSAT]</span></td></tr>
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<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=4c55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c55 OCA], [http://pdbe.org/4c55 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c55 RCSB], [http://www.ebi.ac.uk/pdbsum/4c55 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c55 ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[[https://www.uniprot.org/uniprot/IGHG4_HUMAN IGHG4_HUMAN]]
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Human IgG4, normally the least abundant of the four subclasses of IgG in serum, displays a number of unique biological properties. It can undergo heavy-chain exchange, also known as Fab-arm exchange (FAE), leading to the formation of monovalent but bispecific antibodies, and it interacts poorly with FcgammaRII and FcgammaRIII, and complement. These properties render IgG4 relatively "non-inflammatory" and have made it a suitable format for therapeutic monoclonal antibody production. However, IgG4 is also known to undergo Fc-mediated aggregation and has been implicated in auto-immune disease pathology. We report here the high-resolution crystal structures, at 1.9 and 2.35A, respectively, of human recombinant and serum-derived IgG4-Fc. These structures reveal conformational variability at the CH3-CH3 interface that may promote FAE and a unique conformation for the FG loop in the CH2 domain that would explain the poor FcgammaRII, FcgammaRIII and C1q binding properties of IgG4 compared with IgG1-IgG3. In contrast to other IgG subclasses, this unique conformation folds the FG loop away from the CH2 domain, precluding any interaction with the lower hinge region, which may further facilitate FAE by destabilisation of the hinge. The crystals of IgG4-Fc also display Fc-Fc packing contacts with very extensive interaction surfaces, involving both a consensus binding site in IgG-Fc at the CH2-CH3 interface and known hydrophobic aggregation motifs. These Fc-Fc interactions are compatible with intact IgG4 molecules and may provide a model for the formation of aggregates of IgG4 that can cause disease pathology in the absence of antigen.
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Structural Determinants of Unique Properties of Human IgG4-Fc.,Davies AM, Rispens T, Ooijevaar-de Heer P, Gould HJ, Jefferis R, Aalberse RC, Sutton BJ J Mol Biol. 2013 Nov 6. pii: S0022-2836(13)00696-7. doi:, 10.1016/j.jmb.2013.10.039. PMID:24211234<ref>PMID:24211234</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4c55" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Aalberse, R C]]
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[[Category: Aalberse RC]]
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[[Category: Davies, A M]]
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[[Category: Davies AM]]
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[[Category: Gould, H J]]
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[[Category: Gould HJ]]
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[[Category: Jefferis, R]]
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[[Category: Jefferis R]]
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[[Category: Ooijevaar-deHeer, P]]
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[[Category: Ooijevaar-deHeer P]]
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[[Category: Rispens, T]]
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[[Category: Rispens T]]
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[[Category: Sutton, B J]]
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[[Category: Sutton BJ]]
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[[Category: Antibody]]
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[[Category: Igg]]
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[[Category: Igg1]]
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[[Category: Immune system]]
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[[Category: Immunoglobulin]]
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Revision as of 17:27, 7 September 2022

Crystal structure of serum-derived human IgG4 Fc

PDB ID 4c55

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