|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the effector protein Tse1 from Pseudomonas aeruginosa== | | ==Structure of the effector protein Tse1 from Pseudomonas aeruginosa== |
| - | <StructureSection load='4fge' size='340' side='right' caption='[[4fge]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4fge' size='340' side='right'caption='[[4fge]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fge]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FGE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fge]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FGE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fgd|4fgd]], [[4fgi|4fgi]]</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=4fge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fge OCA], [https://pdbe.org/4fge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fge RCSB], [https://www.ebi.ac.uk/pdbsum/4fge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fge ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA1844 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</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=4fge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fge OCA], [http://pdbe.org/4fge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fge RCSB], [http://www.ebi.ac.uk/pdbsum/4fge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fge ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TSE1_PSEAE TSE1_PSEAE] Toxin secreted by the H1 type VI (H1-T6SS) secretion system into the periplasm of recipient cells. Degrades peptidoglycan via amidase activity thereby helping itself to compete with other bacteria (PubMed:21776080, PubMed:22931054, PubMed:22813741, PubMed:22700987). To protect itself, the bacterium synthesizes immunity protein Tsi1 that specifically interacts with and inactivates cognate toxin (PubMed:21776080, PubMed:22931054, PubMed:22700987).<ref>PMID:21776080</ref> <ref>PMID:22700987</ref> <ref>PMID:22813741</ref> <ref>PMID:22931054</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pseae]] | + | [[Category: Large Structures]] |
| - | [[Category: Barends, T R.M]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Benz, J]] | + | [[Category: Barends TRM]] |
| - | [[Category: Meinhart, A]] | + | [[Category: Benz J]] |
| - | [[Category: Sendlmeier, C]] | + | [[Category: Meinhart A]] |
| - | [[Category: Cytosol]]
| + | [[Category: Sendlmeier C]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: N1pc/p60 superfamily]]
| + | |
| - | [[Category: Peptidoglycan hydrolase]]
| + | |
| Structural highlights
Function
TSE1_PSEAE Toxin secreted by the H1 type VI (H1-T6SS) secretion system into the periplasm of recipient cells. Degrades peptidoglycan via amidase activity thereby helping itself to compete with other bacteria (PubMed:21776080, PubMed:22931054, PubMed:22813741, PubMed:22700987). To protect itself, the bacterium synthesizes immunity protein Tsi1 that specifically interacts with and inactivates cognate toxin (PubMed:21776080, PubMed:22931054, PubMed:22700987).[1] [2] [3] [4]
Publication Abstract from PubMed
During an interbacterial battle, the type-6-secretion-system (T6SS) of the human pathogen Pseudomonas aeruginosa injects the peptidoglycan(PG)-hydrolase Tse1 into the periplasm of Gram-negative enemy cells and induces their lysis. However, for its own benefit, P. aeruginosa produces and transports the immunity-protein Tsi1 into its own periplasm where in prevents accidental exo- and endogenous intoxication. Here we present the high-resolution X-ray crystal structure of the lytic enzyme Tse1 and describe the mechanism by which Tse1 cleaves the gamma-D-glutamyl-l-meso-diaminopimelic acid amide bond of crosslinked PG. Tse1 belongs to the superfamily of N1pC/P60 peptidases but is unique among described members of this family of which the structure was described, since it is a single domain protein without any putative localization domain. Most importantly, we present the crystal structure of Tse1 bound to its immunity-protein Tsi1 as well and describe the mechanism of enzyme inhibition. Tsi1 occludes the active site of Tse1 and abolishes its enzyme activity by forming a hydrogen bond to a catalytically important histidine residue in Tse1. Based on our structural findings in combination with a bioinfomatic approach we also identified a related system in Burkholderia phytofirmans. Not only do our findings point to a common catalytic mechanism of the Tse1 PG-hydrolases, but we can also show that it is distinct from other members of this superfamily. Furthermore, we provide strong evidence that the mechanism of enzyme inhibition between Tsi1 orthologues is conserved. This work is the first structural description of an entire effector/immunity pair injected by the T6SS system. Moreover, it is also the first example of a member of the N1pC/P60 superfamily which becomes inhibited upon binding to its cognate immunity protein.
Structural Insights into the Effector - Immunity System Tse1/Tsi1 from Pseudomonas aeruginosa.,Benz J, Sendlmeier C, Barends TR, Meinhart A PLoS One. 2012;7(7):e40453. Epub 2012 Jul 6. PMID:22792331[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Russell AB, Hood RD, Bui NK, LeRoux M, Vollmer W, Mougous JD. Type VI secretion delivers bacteriolytic effectors to target cells. Nature. 2011 Jul 20;475(7356):343-7. doi: 10.1038/nature10244. PMID:21776080 doi:http://dx.doi.org/10.1038/nature10244
- ↑ Ding J, Wang W, Feng H, Zhang Y, Wang DC. Structural insights into the Pseudomonas aeruginosa type VI virulence effector Tse1 bacteriolysis and self-protection mechanisms. J Biol Chem. 2012 Jun 14. PMID:22700987 doi:10.1074/jbc.M112.368043
- ↑ Chou S, Bui NK, Russell AB, Lexa KW, Gardiner TE, LeRoux M, Vollmer W, Mougous JD. Structure of a peptidoglycan amidase effector targeted to Gram-negative bacteria by the type VI secretion system. Cell Rep. 2012 Jun 28;1(6):656-64. Epub 2012 May 31. PMID:22813741 doi:http://dx.doi.org/10.1016/j.celrep.2012.05.016
- ↑ Shang G, Liu X, Lu D, Zhang J, Li N, Zhu C, Liu S, Yu Q, Zhao Y, Zhang H, Hu J, Cang H, Xu S, Gu L. Structural insight into functioning of Pseudomonas aeruginosa peptidoglycan-hydolase Tse1 and its immunity protein Tsi1. Biochem J. 2012 Aug 29. PMID:22931054 doi:10.1042/BJ20120668
- ↑ Benz J, Sendlmeier C, Barends TR, Meinhart A. Structural Insights into the Effector - Immunity System Tse1/Tsi1 from Pseudomonas aeruginosa. PLoS One. 2012;7(7):e40453. Epub 2012 Jul 6. PMID:22792331 doi:10.1371/journal.pone.0040453
|
