View source for 6wgl


==Dupilumab fab with Crystal Kappa design complexed with human IL-4 receptor==
<StructureSection load='6wgl' size='340' side='right'caption='[[6wgl]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wgl]] is a 3 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=6WGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WGL 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]] 2.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=6wgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wgl OCA], [https://pdbe.org/6wgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wgl RCSB], [https://www.ebi.ac.uk/pdbsum/6wgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wgl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IL4RA_HUMAN IL4RA_HUMAN] Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.<ref>PMID:8124718</ref>   Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.<ref>PMID:8124718</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibody therapeutics are one of the most important classes of drugs. Antibody structures have become an integral part of predicting the behavior of potential therapeutics, either directly or as the basis of modeling. Structures of Fab:antigen complexes have even greater value. While the crystallization and structure determination of Fabs is easy relative to many other protein classes, especially membrane proteins, broad screening and optimization of crystalline hits is still necessary. Through a comprehensive review of rabbit Fab crystal contacts and their incompatibility with human Fabs, we identified a small secondary structural element from the rabbit light chain constant domain potentially responsible for hindering the crystallization of human Fabs. Upon replacing the human kappa constant domain FG loop (HQGLSSP) with the two residue shorter rabbit loop (QGTTS), we dramatically improved the crystallization of human Fabs and Fab:antigen complexes. Our design, which we call "Crystal Kappa", enables rapid crystallization of human fabs and fab complexes in a broad range of conditions, with less material in smaller screens or from dilute solutions.

Rapid and robust antibody Fab fragment crystallization utilizing edge-to-edge beta-sheet packing.,Lieu R, Antonysamy S, Druzina Z, Ho C, Kang NR, Pustilnik A, Wang J, Atwell S PLoS One. 2020 Sep 11;15(9):e0232311. doi: 10.1371/journal.pone.0232311., eCollection 2020. PMID:32915778<ref>PMID:32915778</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wgl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Antonysamy S]]
[[Category: Atwell S]]
[[Category: Benach J]]
[[Category: Druzina Z]]
[[Category: Hendle J]]
[[Category: Ho C]]
[[Category: Lieu R]]
[[Category: Pustilnik A]]
[[Category: Wang J]]