1zms
From Proteopedia
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==LMP1 Protein binds to TRAF3 as a structural CD40== | ==LMP1 Protein binds to TRAF3 as a structural CD40== | ||
| - | <StructureSection load='1zms' size='340' side='right' caption='[[1zms]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='1zms' size='340' side='right'caption='[[1zms]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1zms]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1zms]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_4_strain_RAJI Human herpesvirus 4 strain RAJI]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZMS FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zms OCA], [https://pdbe.org/1zms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zms RCSB], [https://www.ebi.ac.uk/pdbsum/1zms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zms ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/TRAF3_HUMAN TRAF3_HUMAN] Defects in TRAF3 are the cause of susceptibility to herpes simplex encephalitis 3 (HSE3) [MIM:[https://omim.org/entry/614849 614849]. A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.<ref>PMID:20832341</ref> |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/TRAF3_HUMAN TRAF3_HUMAN] Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.<ref>PMID:15383523</ref> <ref>PMID:15084608</ref> <ref>PMID:17991829</ref> <ref>PMID:20097753</ref> <ref>PMID:20185819</ref> <ref>PMID:19937093</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zm/1zms_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zm/1zms_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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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=1zms ConSurf]. | </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=1zms ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Epstein-Barr virus is a human herpesvirus that causes infectious mononucleosis and lymphoproliferative malignancies. LMP1 (latent membrane protein-1), which is encoded by this virus and which is essential for transformation of B lymphocytes, acts as a constitutively active mimic of the tumor necrosis factor receptor (TNFR) CD40. LMP1 is an integral membrane protein containing six transmembrane segments and a cytoplasmic domain at the C terminus that binds to intracellular TNFR-associated factors (TRAFs). TRAFs are intracellular co-inducers of downstream signaling from CD40 and other TNFRs, and TRAF3 is required for activation of B lymphocytes by LMP1. Cytoplasmic C-terminal activation region 1 of LMP1 bears a motif (PQQAT) that conforms to the TRAF recognition motif PVQET in CD40. In this study, we report the crystal structure of this portion of LMP1 C-terminal activation region-1 (204PQQATDD210) bound in complex with TRAF3. The PQQAT motif is bound in the same binding crevice on TRAF3 where CD40 is bound, providing a molecular mechanism for LMP1 to act as a CD40 decoy for TRAF3. The LMP1 motif is presented in the TRAF3 crevice as a close structural mimic of the PVQET motif in CD40, and the intermolecular contacts are similar. However, the viral protein makes a unique contact: a hydrogen bond network formed between Asp210 in LMP1 and Tyr395 and Arg393 in TRAF3. This intermolecular contact is not made in the CD40-TRAF3 complex. The additional hydrogen bonds may stabilize the complex and strengthen the binding to permit LMP1 to compete with CD40 for binding to the TRAF3 crevice, influencing downstream signaling to B lymphocytes and contributing to dysregulated signaling by LMP1. | ||
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| - | LMP1 protein from the Epstein-Barr virus is a structural CD40 decoy in B lymphocytes for binding to TRAF3.,Wu S, Xie P, Welsh K, Li C, Ni CZ, Zhu X, Reed JC, Satterthwait AC, Bishop GA, Ely KR J Biol Chem. 2005 Sep 30;280(39):33620-6. Epub 2005 Jul 11. PMID:16009714<ref>PMID:16009714</ref> | ||
| - | + | ==See Also== | |
| - | + | *[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bishop | + | [[Category: Human herpesvirus 4 strain RAJI]] |
| - | [[Category: Ely | + | [[Category: Large Structures]] |
| - | [[Category: Li | + | [[Category: Bishop GA]] |
| - | [[Category: Ni | + | [[Category: Ely KR]] |
| - | [[Category: Reed | + | [[Category: Li C]] |
| - | [[Category: Satterthwait | + | [[Category: Ni C-Z]] |
| - | [[Category: Welsh | + | [[Category: Reed JC]] |
| - | [[Category: Wu | + | [[Category: Satterthwait AC]] |
| - | [[Category: Xie | + | [[Category: Welsh K]] |
| - | [[Category: Zhu | + | [[Category: Wu SD]] |
| - | + | [[Category: Xie P]] | |
| - | + | [[Category: Zhu X]] | |
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Current revision
LMP1 Protein binds to TRAF3 as a structural CD40
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Categories: Homo sapiens | Human herpesvirus 4 strain RAJI | Large Structures | Bishop GA | Ely KR | Li C | Ni C-Z | Reed JC | Satterthwait AC | Welsh K | Wu SD | Xie P | Zhu X
