1lb6: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 1: Line 1:
==TRAF6-CD40 Complex==
==TRAF6-CD40 Complex==
<StructureSection load='1lb6' size='340' side='right' caption='[[1lb6]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='1lb6' size='340' side='right'caption='[[1lb6]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1lb6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LB6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LB6 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1lb6]] is a 2 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=1LB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LB6 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lb4|1lb4]], [[1lb5|1lb5]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRAF6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CD40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1lb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lb6 OCA], [https://pdbe.org/1lb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lb6 RCSB], [https://www.ebi.ac.uk/pdbsum/1lb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lb6 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lb6 OCA], [http://pdbe.org/1lb6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lb6 RCSB], [http://www.ebi.ac.uk/pdbsum/1lb6 PDBsum]</span></td></tr>
</table>
</table>
== Disease ==
[[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> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TRAF6_HUMAN TRAF6_HUMAN]] E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.<ref>PMID:8837778</ref> <ref>PMID:11057907</ref> <ref>PMID:16378096</ref> <ref>PMID:17135271</ref> <ref>PMID:18093978</ref> <ref>PMID:18758450</ref> <ref>PMID:19675569</ref> <ref>PMID:19713527</ref> <ref>PMID:12140561</ref> <ref>PMID:19465916</ref> [[http://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Receptor for TNFSF5/CD40LG.
[https://www.uniprot.org/uniprot/TRAF6_HUMAN TRAF6_HUMAN] E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.<ref>PMID:8837778</ref> <ref>PMID:11057907</ref> <ref>PMID:16378096</ref> <ref>PMID:17135271</ref> <ref>PMID:18093978</ref> <ref>PMID:18758450</ref> <ref>PMID:19675569</ref> <ref>PMID:19713527</ref> <ref>PMID:12140561</ref> <ref>PMID:19465916</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/lb/1lb6_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/1lb6_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>
Line 21: Line 19:
</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=1lb6 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=1lb6 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tumour-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is the only TRAF family member that participates in signal transduction of both the TNF receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily; it is important for adaptive immunity, innate immunity and bone homeostasis. Here we report crystal structures of TRAF6, alone and in complex with TRAF6-binding peptides from CD40 and TRANCE-R (also known as RANK), members of the TNFR superfamily, to gain insight into the mechanism by which TRAF6 mediates several signalling cascades. A 40 degrees difference in the directions of the bound peptides in TRAF6 and TRAF2 shows that there are marked structural differences between receptor recognition by TRAF6 and other TRAFs. The structural determinant of the petide TRAF6 interaction reveals a Pro-X-Glu-X-X-(aromatic/acidic residue) TRAF6-binding motif, which is present not only in CD40 and TRANCE-R but also in the three IRAK adapter kinases for IL-1R/TLR signalling. Cell-permeable peptides with the TRAF6-binding motif inhibit TRAF6 signalling, which indicates their potential as therapeutic modulators. Our studies identify a universal mechanism by which TRAF6 regulates several signalling cascades in adaptive immunity, innate immunity and bone homeostasis.
Distinct molecular mechanism for initiating TRAF6 signalling.,Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, Segal D, Dzivenu OK, Vologodskaia M, Yim M, Du K, Singh S, Pike JW, Darnay BG, Choi Y, Wu H Nature. 2002 Jul 25;418(6896):443-7. PMID:12140561<ref>PMID:12140561</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1lb6" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[TNF receptor-associated factor|TNF receptor-associated factor]]
*[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Arron, J R]]
[[Category: Large Structures]]
[[Category: Choi, Y]]
[[Category: Arron JR]]
[[Category: Cirilli, M]]
[[Category: Choi Y]]
[[Category: Darnay, B G]]
[[Category: Cirilli M]]
[[Category: Du, K]]
[[Category: Darnay BG]]
[[Category: Dzivenu, O]]
[[Category: Du K]]
[[Category: Kobayashi, T]]
[[Category: Dzivenu O]]
[[Category: Lamothe, B]]
[[Category: Kobayashi T]]
[[Category: Pike, J W]]
[[Category: Lamothe B]]
[[Category: Segal, D]]
[[Category: Pike JW]]
[[Category: Shevde, N K]]
[[Category: Segal D]]
[[Category: Singh, S]]
[[Category: Shevde NK]]
[[Category: Vologodskaia, M]]
[[Category: Singh S]]
[[Category: Wu, H]]
[[Category: Vologodskaia M]]
[[Category: Ye, H]]
[[Category: Wu H]]
[[Category: Yim, M]]
[[Category: Ye H]]
[[Category: Signaling protein]]
[[Category: Yim M]]
[[Category: Traf6-cd40 complex]]
Retrieved from "https://proteopedia.org/1lb6"