3ub3: Difference between revisions

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==D96N variant of TIR domain of Mal/TIRAP==
==D96N variant of TIR domain of Mal/TIRAP==
<StructureSection load='3ub3' size='340' side='right' caption='[[3ub3]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
<StructureSection load='3ub3' size='340' side='right' caption='[[3ub3]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3ub3]] is a 1 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=3UB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UB3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3ub3]] is a 1 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=3UB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UB3 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ub2|3ub2]], [[3ub4|3ub4]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ub2|3ub2]], [[3ub4|3ub4]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TIRAP, MAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TIRAP, MAL ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ub3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ub3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ub3 RCSB], [http://www.ebi.ac.uk/pdbsum/3ub3 PDBsum]</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=3ub3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ub3 OCA], [http://pdbe.org/3ub3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ub3 RCSB], [http://www.ebi.ac.uk/pdbsum/3ub3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ub3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 3ub3" style="background-color:#fffaf0;"></div>
==See Also==
*[[TIR domain-containing adaptor protein|TIR domain-containing adaptor protein]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Lin, Z]]
[[Category: Lin, Z]]
[[Category: Shen, Y]]
[[Category: Shen, Y]]

Revision as of 14:51, 4 August 2016

D96N variant of TIR domain of Mal/TIRAPD96N variant of TIR domain of Mal/TIRAP

Structural highlights

3ub3 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:TIRAP, MAL (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TIRAP_HUMAN] Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6.[1] [2]

Publication Abstract from PubMed

MyD88 adaptor-like protein (Mal) is a crucial adaptor that acts as a bridge to recruit the MyD88 molecule to activated TLR4 receptors in response to invading pathogens. The specific assembly of the Toll/interleukin-1 receptor (TIR) domains of TLR4, Mal and MyD88 is responsible for proper signal transduction in the TLR4 signaling pathway. However, the molecular mechanism for the specificity of these TIR domains remains unclear. Here, we present the crystal structure of the TIR domain of the human Mal molecule (Mal-TIR) at a resolution of 2.4 A. Unexpectedly, Mal-TIR exhibits an extraordinarily long AB loop, but no alphaB helix or BB loop, distinguishing it from other TIR domains. More importantly, the Mal-TIR AB loop is capable of mediating direct binding to the TIR domains of TLR4 and MyD88 simultaneously. We also found that Mal-TIR can form a back-to-back dimer that may resemble the dimeric assembly of the entire Mal molecule. Our data demonstrate the bridge role of the Mal-TIR domain and provide important information about TIR domain specificity.

Structural insights into TIR domain specificity of the bridging adaptor Mal in TLR4 signaling.,Lin Z, Lu J, Zhou W, Shen Y PLoS One. 2012;7(4):e34202. Epub 2012 Apr 2. PMID:22485159[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Semaan N, Alsaleh G, Gottenberg JE, Wachsmann D, Sibilia J. Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways. J Immunol. 2008 Mar 1;180(5):3485-91. PMID:18292575
  2. Nagpal K, Plantinga TS, Wong J, Monks BG, Gay NJ, Netea MG, Fitzgerald KA, Golenbock DT. A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling. J Biol Chem. 2009 Sep 18;284(38):25742-8. doi: 10.1074/jbc.M109.014886. Epub 2009, Jun 9. PMID:19509286 doi:http://dx.doi.org/10.1074/jbc.M109.014886
  3. Lin Z, Lu J, Zhou W, Shen Y. Structural insights into TIR domain specificity of the bridging adaptor Mal in TLR4 signaling. PLoS One. 2012;7(4):e34202. Epub 2012 Apr 2. PMID:22485159 doi:10.1371/journal.pone.0034202

3ub3, resolution 2.75Å

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