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| | ==Structure of the TIR domain of the immunosuppressor BtpA from Brucella== | | ==Structure of the TIR domain of the immunosuppressor BtpA from Brucella== |
| - | <StructureSection load='4lzp' size='340' side='right' caption='[[4lzp]], [[Resolution|resolution]] 3.15Å' scene=''> | + | <StructureSection load='4lzp' size='340' side='right'caption='[[4lzp]], [[Resolution|resolution]] 3.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lzp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Brumb Brumb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LZP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lzp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Brucella_melitensis_ATCC_23457 Brucella melitensis ATCC 23457]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LZP FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3h16|3h16]]</td></tr> | + | </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=4lzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lzp OCA], [https://pdbe.org/4lzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lzp RCSB], [https://www.ebi.ac.uk/pdbsum/4lzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lzp ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BMEA_A0279 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=546272 BRUMB])</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=4lzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lzp OCA], [http://pdbe.org/4lzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lzp RCSB], [http://www.ebi.ac.uk/pdbsum/4lzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lzp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BTPA_BRUMB BTPA_BRUMB] Virulence factor that interferes with host Toll-like receptor 2 (TLR2) and TLR4 signaling, resulting in the reduction of dendritic cell maturation, inhibition of pro-inflammatory cytokine secretion and impaired NF-kappa-B activation in macrophages (PubMed:18266466). Acts as a NAD(+) hydrolase (NADase) by catalyzing cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide (PubMed:29395922). In addition to ADPR, also generates a cyclization variant of cyclic ADPR (cADPR), termed v-cADPR, for which the cyclizing bond is unknown (PubMed:29395922).<ref>PMID:18266466</ref> <ref>PMID:29395922</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brumb]] | + | [[Category: Brucella melitensis ATCC 23457]] |
| - | [[Category: Kaplan-turkoz, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Terradot, L]] | + | [[Category: Kaplan-turkoz B]] |
| - | [[Category: Vergunst, A]] | + | [[Category: O'callaghan D]] |
| - | [[Category: Callaghan, D O]]
| + | [[Category: Terradot L]] |
| - | [[Category: Immune system]] | + | [[Category: Vergunst A]] |
| - | [[Category: Membrane]] | + | |
| - | [[Category: Myd88]]
| + | |
| - | [[Category: Tir domain]]
| + | |
| - | [[Category: Virulence factor immuno suppressor]]
| + | |
| Structural highlights
Function
BTPA_BRUMB Virulence factor that interferes with host Toll-like receptor 2 (TLR2) and TLR4 signaling, resulting in the reduction of dendritic cell maturation, inhibition of pro-inflammatory cytokine secretion and impaired NF-kappa-B activation in macrophages (PubMed:18266466). Acts as a NAD(+) hydrolase (NADase) by catalyzing cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide (PubMed:29395922). In addition to ADPR, also generates a cyclization variant of cyclic ADPR (cADPR), termed v-cADPR, for which the cyclizing bond is unknown (PubMed:29395922).[1] [2]
Publication Abstract from PubMed
BtpA/Btp1/TcpB is a virulence factor produced by Brucella species that possesses a Toll interleukin-1 receptor (TIR) domain. Once delivered into the host cell, BtpA interacts with MyD88 to interfere with TLR signalling and modulates microtubule dynamics. Here the crystal structure of the BtpA TIR domain at 3.15A is presented. The structure shows a dimeric arrangement of a canonical TIR domain, similar to the Paracoccus denitrificans Tir protein but secured by a unique long N-terminal alpha-tail that packs against the TIR:TIR dimer. Structure-based mutations and multi-angle light scattering experiments characterized the BtpA dimer conformation in solution. The structure of BtpA will help with studies to understand the mechanisms involved in its interactions with MyD88 and with microtubules.
Structure of the Toll/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA/Btp1/TcpB.,Kaplan-Turkoz B, Koelblen T, Felix C, Candusso MP, O'Callaghan D, Vergunst AC, Terradot L FEBS Lett. 2013 Nov 1;587(21):3412-6. doi: 10.1016/j.febslet.2013.09.007. Epub, 2013 Sep 25. PMID:24076024[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Salcedo SP, Marchesini MI, Lelouard H, Fugier E, Jolly G, Balor S, Muller A, Lapaque N, Demaria O, Alexopoulou L, Comerci DJ, Ugalde RA, Pierre P, Gorvel JP. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog. 2008 Feb 8;4(2):e21. doi: 10.1371/journal.ppat.0040021. PMID:18266466 doi:http://dx.doi.org/10.1371/journal.ppat.0040021
- ↑ Essuman K, Summers DW, Sasaki Y, Mao X, Yim AKY, DiAntonio A, Milbrandt J. TIR Domain Proteins Are an Ancient Family of NAD(+)-Consuming Enzymes. Curr Biol. 2018 Feb 5;28(3):421-430.e4. doi: 10.1016/j.cub.2017.12.024. Epub 2018 , Jan 25. PMID:29395922 doi:http://dx.doi.org/10.1016/j.cub.2017.12.024
- ↑ Kaplan-Turkoz B, Koelblen T, Felix C, Candusso MP, O'Callaghan D, Vergunst AC, Terradot L. Structure of the Toll/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA/Btp1/TcpB. FEBS Lett. 2013 Nov 1;587(21):3412-6. doi: 10.1016/j.febslet.2013.09.007. Epub, 2013 Sep 25. PMID:24076024 doi:http://dx.doi.org/10.1016/j.febslet.2013.09.007
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