4lqc: Difference between revisions

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==The crystal structures of the Brucella protein TcpB and the TLR adaptor protein TIRAP show structural differences in microbial TIR mimicry.==
==The crystal structures of the Brucella protein TcpB and the TLR adaptor protein TIRAP show structural differences in microbial TIR mimicry.==
<StructureSection load='4lqc' size='340' side='right' caption='[[4lqc]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='4lqc' size='340' side='right'caption='[[4lqc]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4lqc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_melitensis"_(hughes_1893)_bruce_1893 "micrococcus melitensis" (hughes 1893) bruce 1893]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LQC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LQC FirstGlance]. <br>
<table><tr><td colspan='2'>[[4lqc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Brucella_melitensis Brucella melitensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LQC FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lqd|4lqd]]</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]] 2.3&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NC_003317 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29459 "Micrococcus melitensis" (Hughes 1893) Bruce 1893])</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=4lqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lqc OCA], [https://pdbe.org/4lqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lqc RCSB], [https://www.ebi.ac.uk/pdbsum/4lqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lqc 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=4lqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lqc OCA], [http://pdbe.org/4lqc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lqc RCSB], [http://www.ebi.ac.uk/pdbsum/4lqc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lqc ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q8YF53_BRUME Q8YF53_BRUME]
The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR) signaling through molecular mimicry. The TIR domain-containing protein TcpB from Brucella inhibits TLR signaling through interaction with host adaptor proteins TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we have determined the X-ray crystal structures of the TIR domains from the Brucella protein TcpB and the host adaptor protein TIRAP. We have further characterized homotypic interactions of TcpB using hydrogen/deuterium exchange mass spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation and NF-kappaB reporter assays. The crystal structure of the TcpB TIR domain reveals the microtubule-binding site encompassing the BB loop as well as a symmetrical dimer mediated by the DD and EE loops. This dimerization interface is validated by peptide mapping through hydrogen/deuterium exchange mass spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N-terminal TIR domain fold containing a disulfide bond formed by Cys(89) and Cys(134). A comparison between the TcpB and TIRAP crystal structures reveals substantial conformational differences in the region that encompasses the BB loop. These findings underscore the similarities and differences in the molecular features found in the microbial and host TIR domains, which suggests mechanisms of bacterial mimicry of host signaling adaptor proteins, such as TIRAP.


Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry.,Snyder GA, Deredge D, Waldhuber A, Fresquez T, Wilkins DZ, Smith PT, Durr S, Cirl C, Jiang J, Jennings W, Luchetti T, Snyder N, Sundberg EJ, Wintrode P, Miethke T, Xiao TS J Biol Chem. 2014 Jan 10;289(2):669-79. doi: 10.1074/jbc.M113.523407. Epub 2013, Nov 25. PMID:24275656<ref>PMID:24275656</ref>
==See Also==
 
*[[TIR domain-containing adapter protein|TIR domain-containing adapter protein]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4lqc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cirl, C]]
[[Category: Brucella melitensis]]
[[Category: Fresquez, T]]
[[Category: Large Structures]]
[[Category: Jiang, J]]
[[Category: Cirl C]]
[[Category: Luchetti, T]]
[[Category: Fresquez T]]
[[Category: Miethke, T]]
[[Category: Jiang J]]
[[Category: Smith, P]]
[[Category: Luchetti T]]
[[Category: Snyder, G A]]
[[Category: Miethke T]]
[[Category: Snyder, N]]
[[Category: Smith P]]
[[Category: Xiao, T S]]
[[Category: Snyder GA]]
[[Category: Bacterial tir like domain]]
[[Category: Snyder N]]
[[Category: Cytoplasmic]]
[[Category: Xiao TS]]
[[Category: Flavodoxin fold]]
[[Category: Immune system]]
[[Category: Innate immunity]]
[[Category: Myd88]]
[[Category: Myd88 binding]]
[[Category: Proteolytic fragment from alpha 2 chymotrypsin]]
[[Category: Tir]]
[[Category: Tirap molecular mimic]]

Latest revision as of 15:21, 1 March 2024

The crystal structures of the Brucella protein TcpB and the TLR adaptor protein TIRAP show structural differences in microbial TIR mimicry.The crystal structures of the Brucella protein TcpB and the TLR adaptor protein TIRAP show structural differences in microbial TIR mimicry.

Structural highlights

4lqc is a 2 chain structure with sequence from Brucella melitensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8YF53_BRUME

See Also

4lqc, resolution 2.30Å

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