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| | ==Mycobacterium tuberculosis Rv1957 SecB-like chaperone in complex with a ChAD peptide from Rv1956 HigA1 antitoxin== | | ==Mycobacterium tuberculosis Rv1957 SecB-like chaperone in complex with a ChAD peptide from Rv1956 HigA1 antitoxin== |
| - | <StructureSection load='5mtw' size='340' side='right' caption='[[5mtw]], [[Resolution|resolution]] 1.84Å' scene=''> | + | <StructureSection load='5mtw' size='340' side='right'caption='[[5mtw]], [[Resolution|resolution]] 1.84Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mtw]] is a 7 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MTW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MTW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mtw]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MTW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></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]] 1.84Å</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=5mtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mtw OCA], [http://pdbe.org/5mtw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mtw RCSB], [http://www.ebi.ac.uk/pdbsum/5mtw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mtw ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></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=5mtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mtw OCA], [https://pdbe.org/5mtw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mtw RCSB], [https://www.ebi.ac.uk/pdbsum/5mtw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mtw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SECBL_MYCTU SECBL_MYCTU]] Chaperone component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Prevents antitoxin HigA1 aggregation in vitro at a 1:3 chaperone:antitoxin ratio, probably also protects antitoxin HigA1 from protease. Required for neutralization of toxin HigB1 upon ectopic expression in Mycobacterium marinum or E.coli. When expressed in E.coli complements a secB deletion, restores export of OmpA and MBP and inhibits aggregation of proOmpC although it is less efficient than endogenous SecB. Complements the general chaperone function of E.coli SecB less well.<ref>PMID:21536872</ref> [[http://www.uniprot.org/uniprot/HIGA1_MYCTU HIGA1_MYCTU]] Antitoxin component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis neutralizes the effect of cognate toxin HigB1. Neutralization of HigB1 toxin in E.coli or M.marinum also requires SecB-like chaperone Rv1957, making this the first toxin-antitoxin chaperone (TAC) system. Antitoxin aggregation and degradation are prevented by the chaperone.<ref>PMID:21536872</ref> In M.tuberculosis represses expression of the Rv1954A-higB1-higA1-Rv1957 operon promoter but not that of the higB1-higA1-Rv1957 operon.<ref>PMID:20585061</ref> | + | [https://www.uniprot.org/uniprot/SECBL_MYCTU SECBL_MYCTU] Chaperone component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Prevents antitoxin HigA1 aggregation in vitro at a 1:3 chaperone:antitoxin ratio, probably also protects antitoxin HigA1 from protease. Required for neutralization of toxin HigB1 upon ectopic expression in Mycobacterium marinum or E.coli. When expressed in E.coli complements a secB deletion, restores export of OmpA and MBP and inhibits aggregation of proOmpC although it is less efficient than endogenous SecB. Complements the general chaperone function of E.coli SecB less well.<ref>PMID:21536872</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | Bacterial toxin-antitoxin (TA) systems, in which a labile antitoxin binds and inhibits the toxin, can promote adaptation and persistence by modulating bacterial growth in response to stress. Some atypical TA systems, known as tripartite toxin-antitoxin-chaperone (TAC) modules, include a molecular chaperone that facilitates folding and protects the antitoxin from degradation. Here we use a TAC module from Mycobacterium tuberculosis as a model to investigate the molecular mechanisms by which classical TAs can become 'chaperone-addicted'. The chaperone specifically binds the antitoxin at a short carboxy-terminal sequence (chaperone addiction sequence, ChAD) that is not present in chaperone-independent antitoxins. In the absence of chaperone, the ChAD sequence destabilizes the antitoxin, thus preventing toxin inhibition. Chaperone-ChAD pairs can be transferred to classical TA systems or to unrelated proteins and render them chaperone-dependent. This mechanism might be used to optimize the expression and folding of heterologous proteins in bacterial hosts for biotechnological or medical purposes.
| + | SecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition. Chaperone dependency is conferred by a C-terminal extension in the antitoxin known as chaperone addiction (ChAD) sequence, which makes the antitoxin aggregation-prone and prevents toxin inhibition. Using TAC of Mycobacterium tuberculosis, we present the structure of a SecB-like chaperone bound to its ChAD peptide. We find differences in the binding interfaces when compared to SecB-SecA or SecB-preprotein complexes, and show that the antitoxin can reach a functional form while bound to the chaperone. This work reveals how chaperones can use discrete surface binding regions to accommodate different clients or partners and thereby expand their substrate repertoire and functions. |
| | | | |
| - | Chaperone addiction of toxin-antitoxin systems.,Bordes P, Sala AJ, Ayala S, Texier P, Slama N, Cirinesi AM, Guillet V, Mourey L, Genevaux P Nat Commun. 2016 Nov 9;7:13339. doi: 10.1038/ncomms13339. PMID:27827369<ref>PMID:27827369</ref>
| + | Structural insights into chaperone addiction of toxin-antitoxin systems.,Guillet V, Bordes P, Bon C, Marcoux J, Gervais V, Sala AJ, Dos Reis S, Slama N, Mares-Mejia I, Cirinesi AM, Maveyraud L, Genevaux P, Mourey L Nat Commun. 2019 Feb 15;10(1):782. doi: 10.1038/s41467-019-08747-4. PMID:30770830<ref>PMID:30770830</ref> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Guillet, V]] | + | [[Category: Large Structures]] |
| - | [[Category: Mourey, L]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Chaperone]] | + | [[Category: Guillet V]] |
| - | [[Category: Complex]] | + | [[Category: Mourey L]] |
| - | [[Category: Toxin-antitoxin-chaperone system]]
| + | |
| Structural highlights
Function
SECBL_MYCTU Chaperone component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Prevents antitoxin HigA1 aggregation in vitro at a 1:3 chaperone:antitoxin ratio, probably also protects antitoxin HigA1 from protease. Required for neutralization of toxin HigB1 upon ectopic expression in Mycobacterium marinum or E.coli. When expressed in E.coli complements a secB deletion, restores export of OmpA and MBP and inhibits aggregation of proOmpC although it is less efficient than endogenous SecB. Complements the general chaperone function of E.coli SecB less well.[1]
Publication Abstract from PubMed
SecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition. Chaperone dependency is conferred by a C-terminal extension in the antitoxin known as chaperone addiction (ChAD) sequence, which makes the antitoxin aggregation-prone and prevents toxin inhibition. Using TAC of Mycobacterium tuberculosis, we present the structure of a SecB-like chaperone bound to its ChAD peptide. We find differences in the binding interfaces when compared to SecB-SecA or SecB-preprotein complexes, and show that the antitoxin can reach a functional form while bound to the chaperone. This work reveals how chaperones can use discrete surface binding regions to accommodate different clients or partners and thereby expand their substrate repertoire and functions.
Structural insights into chaperone addiction of toxin-antitoxin systems.,Guillet V, Bordes P, Bon C, Marcoux J, Gervais V, Sala AJ, Dos Reis S, Slama N, Mares-Mejia I, Cirinesi AM, Maveyraud L, Genevaux P, Mourey L Nat Commun. 2019 Feb 15;10(1):782. doi: 10.1038/s41467-019-08747-4. PMID:30770830[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bordes P, Cirinesi AM, Ummels R, Sala A, Sakr S, Bitter W, Genevaux P. SecB-like chaperone controls a toxin-antitoxin stress-responsive system in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8438-43. doi:, 10.1073/pnas.1101189108. Epub 2011 May 2. PMID:21536872 doi:http://dx.doi.org/10.1073/pnas.1101189108
- ↑ Guillet V, Bordes P, Bon C, Marcoux J, Gervais V, Sala AJ, Dos Reis S, Slama N, Mares-Mejia I, Cirinesi AM, Maveyraud L, Genevaux P, Mourey L. Structural insights into chaperone addiction of toxin-antitoxin systems. Nat Commun. 2019 Feb 15;10(1):782. doi: 10.1038/s41467-019-08747-4. PMID:30770830 doi:http://dx.doi.org/10.1038/s41467-019-08747-4
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