View source for 5ihl


==STRUCTURE OF THE EXTRACELLULAR DOMAIN OF THE CD40 IN COMPLEX WITH 3H56-5 DAB==
<StructureSection load='5ihl' size='340' side='right'caption='[[5ihl]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ihl]] is a 8 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=5IHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IHL 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5ihl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ihl OCA], [https://pdbe.org/5ihl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ihl RCSB], [https://www.ebi.ac.uk/pdbsum/5ihl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ihl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN] Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:[https://omim.org/entry/606843 606843]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:11675497</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN] Receptor for TNFSF5/CD40LG.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Current clinical anti-CD40 biologic agents include both antagonist molecules for the treatment of autoimmune diseases, and agonist molecules for immuno-oncology, yet the relationship between CD40 epitope and these opposing biological outcomes is not well defined. This report describes the identification of potent antagonist domain antibodies (dAbs) that bind to a novel human-CD40 specific epitope which is divergent in the CD40 of non-human primates. A similarly selected anti-cynomolgus-CD40 dAb recognizing the homologous epitope is also a potent antagonist. Mutagenesis, biochemical, and X-ray crystallography studies demonstrate that the epitope is distinct from that of CD40 agonists. Both the human-specific and cynomolgus-specific molecules remain pure antagonists even when formatted as bivalent Fc-fusion proteins, making this an attractive therapeutic format for targeting hCD40 in autoimmune indications.

Functional antagonism of human CD40 achieved by targeting a unique species-specific epitope.,Yamniuk AP, Suri A, Krystek SR, Tamura J, Ramamurthy V, Kuhn R, Carroll K, Fleener C, Ryseck R, Cheng L, An Y, Drew P, Grant S, Suchard SJ, Nadler SG, Bryson JW, Sheriff S J Mol Biol. 2016 May 21. pii: S0022-2836(16)30169-3. doi:, 10.1016/j.jmb.2016.05.014. PMID:27216500<ref>PMID:27216500</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ihl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
*[[3D structures of human antibody|3D structures of human antibody]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sheriff S]]