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1aly

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[[Image:1aly.gif|left|200px]]<br /><applet load="1aly" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1aly, resolution 2.00&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND==
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BACKGROUND: The CD40 ligand (CD40L) is a member of the tumor necrosis factor (TNF) family of proteins and is transiently expressed on the surface of activated T cells. The binding of CD40L to CD40, which is expressed on the surface of B cells, provides a critical and unique pathway of cellular activation resulting in antibody isotype switching, regulation of apoptosis, and B cell proliferation and differentiation. Naturally occurring mutations of CD40L result in the clinical hyper-IgM syndrome, characterized by an inability to produce immunoglobulins of the IgG, IgA and IgE isotypes. RESULTS: We have determined the crystal structure of a soluble extracellular fragment of human CD40L to 2 A resolution and with an R factor of 21.8%. Although the molecule forms a trimer similar to that found for other members of the TNF family, such as TNF alpha and lymphotoxin-alpha, and exhibits a similar overall fold, there are considerable differences in several loops including those predicted to be involved in CD40 binding. CONCLUSIONS: The structure suggests that most of the hyper-IgM syndrome mutations affect the folding and stability of the molecule rather than the CD40-binding site directly. Despite the fact that the hyper-IgM syndrome mutations are dispersed in the primary sequence, a large fraction of them are clustered in space in the vicinity of a surface loop, close to the predicted CD40-binding site.
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<StructureSection load='1aly' size='340' side='right'caption='[[1aly]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1aly]] is a 1 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=1ALY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ALY 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]] 2&#8491;</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=1aly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aly OCA], [https://pdbe.org/1aly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aly RCSB], [https://www.ebi.ac.uk/pdbsum/1aly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aly ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://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:[https://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>
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== Function ==
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[https://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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/al/1aly_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1aly ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Immunodeficiency, X-linked, with hyper-IgM OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300386 300386]], Transposition of the great arteries, dextro-looped 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608771 608771]]
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*[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]]
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*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
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==About this Structure==
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== References ==
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1ALY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of 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=1ALY OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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2 A crystal structure of an extracellular fragment of human CD40 ligand., Karpusas M, Hsu YM, Wang JH, Thompson J, Lederman S, Chess L, Thomas D, Structure. 1995 Oct 15;3(10):1031-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8589998 8589998]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Hsu, Y M.]]
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[[Category: Hsu YM]]
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[[Category: Karpusas, M.]]
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[[Category: Karpusas M]]
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[[Category: Thomas, D.]]
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[[Category: Thomas D]]
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[[Category: cd40 ligand]]
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[[Category: cd40l]]
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[[Category: cytokine]]
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[[Category: hyper-igm syndrome]]
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[[Category: tnf]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:55 2008''
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Current revision

CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND

PDB ID 1aly

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