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3qd6

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{{STRUCTURE_3qd6| PDB=3qd6 | SCENE= }}
 
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===Crystal structure of the CD40 and CD154 (CD40L) complex===
 
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{{ABSTRACT_PUBMED_21285457}}
 
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==Disease==
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==Crystal structure of the CD40 and CD154 (CD40L) complex==
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[[http://www.uniprot.org/uniprot/CD40L_HUMAN CD40L_HUMAN]] Defects in CD40LG are the cause of X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) [MIM:[http://omim.org/entry/308230 308230]]; also known as X-linked hyper IgM syndrome (XHIM). HIGM1 is an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.<ref>PMID:7678782</ref><ref>PMID:7679206</ref><ref>PMID:8094231</ref><ref>PMID:7679801</ref><ref>PMID:7717401</ref><ref>PMID:7532185</ref><ref>PMID:8889581</ref><ref>PMID:8550833</ref><ref>PMID:9150729</ref><ref>PMID:9746782</ref> [[http://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:[http://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>
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<StructureSection load='3qd6' size='340' side='right'caption='[[3qd6]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3qd6]] is a 10 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=3QD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QD6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qd6 OCA], [https://pdbe.org/3qd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qd6 RCSB], [https://www.ebi.ac.uk/pdbsum/3qd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qd6 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN] Receptor for TNFSF5/CD40LG.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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CD40 is a tumor necrosis factor receptor (TNFR) family protein that plays an important role in B cell development. CD154/CD40L is the physiological ligand of CD40. We have determined the crystal structure of the CD40-CD154 complex at 3.5 A resolution. The binding site of CD40 is located in a crevice formed between two CD154 subunits. Charge complementarity plays a critical role in the CD40-CD154 interaction. Some of the missense mutations found in hereditary hyper-IgM syndrome can be mapped to the CD40-CD154 interface. The CD40 interaction area of one of the CD154 subunits is twice as large as that of the other subunit forming the binding crevice. This is because cysteine-rich domain 3 (CRD3) of CD40 has a disulfide bridge in an unusual position that alters the direction of the ladder-like structure of CD40. The Ser(132) loop of CD154 is not involved in CD40 binding but its substitution significantly reduces p38- and ERK-dependent signaling by CD40, whereas JNK-dependent signaling is not affected. These findings suggest that ligand-induced di- or trimerization is necessary but not sufficient for complete activation of CD40.
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==Function==
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Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation.,An HJ, Kim YJ, Song DH, Park BS, Kim HM, Lee JD, Paik SG, Lee JO, Lee H J Biol Chem. 2011 Apr 1;286(13):11226-35. Epub 2011 Feb 1. PMID:21285457<ref>PMID:21285457</ref>
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[[http://www.uniprot.org/uniprot/CD40L_HUMAN CD40L_HUMAN]] Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL-4. Involved in immunoglobulin class switching.<ref>PMID:15193700</ref> Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.<ref>PMID:15193700</ref> [[http://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Receptor for TNFSF5/CD40LG.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3qd6]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QD6 OCA].
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</div>
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<div class="pdbe-citations 3qd6" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:021285457</ref><references group="xtra"/><references/>
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*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Kim, H M.]]
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[[Category: Large Structures]]
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[[Category: Kim, Y J.]]
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[[Category: Kim HM]]
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[[Category: Lee, J O.]]
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[[Category: Kim YJ]]
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[[Category: Park, B S.]]
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[[Category: Lee J-O]]
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[[Category: Song, D H.]]
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[[Category: Park BS]]
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[[Category: Cytokine-cytokine receptor complex]]
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[[Category: Song DH]]
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[[Category: Immune regulator]]
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[[Category: Receptor]]
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Current revision

Crystal structure of the CD40 and CD154 (CD40L) complex

PDB ID 3qd6

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