View source for 6wyt


==Crystal structure of anti-Muscle Specific Kinase (MuSK) Fab, MuSK1B==
<StructureSection load='6wyt' size='340' side='right'caption='[[6wyt]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wyt]] 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=6WYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYT 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6wyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyt OCA], [https://pdbe.org/6wyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyt RCSB], [https://www.ebi.ac.uk/pdbsum/6wyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyt ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pathogenic muscle-specific tyrosine kinase (MuSK)-specific IgG4 autoantibodies in autoimmune myasthenia gravis (MG) are functionally monovalent as a result of Fab-arm exchange. The development of these unique autoantibodies is not well understood. We examined MG patient-derived monoclonal autoantibodies (mAbs), their corresponding germline-encoded unmutated common ancestors (UCAs), and monovalent antigen-binding fragments (Fabs) to investigate how affinity maturation contributes to binding and immunopathology. Mature mAbs, UCA mAbs, and mature monovalent Fabs bound to MuSK and demonstrated pathogenic capacity. However, monovalent UCA Fabs bound to MuSK but did not have measurable pathogenic capacity. Affinity of the UCA Fabs for MuSK was 100-fold lower than the subnanomolar affinity of the mature Fabs. Crystal structures of two Fabs revealed how mutations acquired during affinity maturation may contribute to increased MuSK-binding affinity. These findings indicate that the autoantigen drives autoimmunity in MuSK MG through the accumulation of somatic mutations such that monovalent IgG4 Fab-arm-exchanged autoantibodies reach a high-affinity threshold required for pathogenic capacity.

Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis.,Fichtner ML, Vieni C, Redler RL, Kolich L, Jiang R, Takata K, Stathopoulos P, Suarez PA, Nowak RJ, Burden SJ, Ekiert DC, O'Connor KC J Exp Med. 2020 Dec 7;217(12):e20200513. doi: 10.1084/jem.20200513. PMID:32820331<ref>PMID:32820331</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wyt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ekiert D]]
[[Category: Vieni C]]