View source for 4c54


==Crystal structure of recombinant human IgG4 Fc==
<StructureSection load='4c54' size='340' side='right'caption='[[4c54]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4c54]] 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=4C54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C54 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</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=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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c54 OCA], [https://pdbe.org/4c54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c54 RCSB], [https://www.ebi.ac.uk/pdbsum/4c54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c54 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IGHG4_HUMAN IGHG4_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4c54" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aalberse RC]]
[[Category: Davies AM]]
[[Category: Gould HJ]]
[[Category: Jefferis R]]
[[Category: Ooijevaar-deHeer P]]
[[Category: Rispens T]]
[[Category: Sutton BJ]]