View source for 7chz


==Crystal Structure Of Human Il-1beta In Complex With Antibody Binding Fragment Of IgG26A==
<StructureSection load='7chz' size='340' side='right'caption='[[7chz]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7chz]] 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=7CHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CHZ 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]] 2.5&#8491;</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=7chz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7chz OCA], [https://pdbe.org/7chz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7chz RCSB], [https://www.ebi.ac.uk/pdbsum/7chz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7chz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interleukin-1beta (IL-1beta) is a potent pleiotropic cytokine playing a central role in protecting cells from microbial pathogen infection or endogenous stress. After it binds to IL-1RI and recruits IL-1 receptor accessory protein (IL-1RAcP), signaling culminates in activation of NF-kappaB. Many pathophysiological diseases have been attributed to the derailment of IL-1beta regulation. Several blocking reagents have been developed based on two mechanisms: blocking the binding of IL-1beta to IL-1RI or inhibiting the recruitment of IL-1RAcP to the IL-1beta initial complex. In order to simultaneously fulfill these two actions, a human anti-IL-1beta neutralizing antibody IgG26 was screened from human genetic phage-display library and furthered structure-optimized to final version, IgG26AW. IgG26AW has a sub-nanomolar binding affinity for human IL-1beta. We validated IgG26AW-neutralizing antibodies specific for IL-1beta in vivo to prevent human IL-1beta-driving IL-6 elevation in C56BL/6 mice. Mice underwent treatments with IgG26AW in A549 and MDA-MB-231 xenograft mouse cancer models have also been observed with tumor shrank and inhibition of tumor metastasis. The region where IgG26 binds to IL-1beta also overlaps with the position where IL-1RI and IL-1RAcP bind, as revealed by the 26-Fab/IL-1beta complex structure. Meanwhile, SPR experiments showed that IL-1beta bound by IgG26AW prevented the further binding of IL-1RI and IL-1RAcP, which confirmed our inference from the result of protein structure. Therefore, the inhibitory mechanism of IgG26AW is to block the assembly of the IL-1beta/IL-1RI/IL-1RAcP ternary complex which further inhibits downstream signaling. Based on its high affinity, high neutralizing potency, and novel binding epitope simultaneously occupying both IL-1RI and IL-1RAcP residues that bind to IL-1beta, IgG26AW may be a new candidate for treatments of inflammation-related diseases or for complementary treatments of cancers in which the role of IL-1beta is critical to pathogenesis.

Structure-based Development of Human Interleukin-1beta-Specific Antibody That Simultaneously Inhibits Binding to Both IL-1RI and IL-1RAcP.,Kuo WC, Lee CC, Chang YW, Pang W, Chen HS, Hou SC, Lo SY, Yang AS, Wang AH J Mol Biol. 2021 Feb 19;433(4):166766. doi: 10.1016/j.jmb.2020.166766. Epub 2020 , Dec 24. PMID:33359099<ref>PMID:33359099</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7chz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kuo WC]]
[[Category: Lee CC]]
[[Category: Wang AHJ]]