6w08: Difference between revisions
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<StructureSection load='6w08' size='340' side='right'caption='[[6w08]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='6w08' size='340' side='right'caption='[[6w08]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6w08]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W08 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6w08]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibch Vibch]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W08 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VC_A0884 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</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=6w08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w08 OCA], [https://pdbe.org/6w08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w08 RCSB], [https://www.ebi.ac.uk/pdbsum/6w08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w08 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Alpha-pore-forming toxins (alpha-PFTs) are secreted by many species of bacteria, including Escherichia coli, Aeromonas hydrophila, and Bacillus thuringiensis, as part of their arsenal of virulence factors, and are often cytotoxic. In particular, for alpha-PFTs, the membrane-spanning channel they form is composed of hydrophobic alpha-helices. These toxins oligomerize at the surface of target cells and transition from a soluble to a protomer state in which they expose their hydrophobic regions and insert into the membrane to form a pore. The pores may be composed of homooligomers of one component or heterooligomers with two or three components, resulting in bi- or tripartite toxins. The multicomponent alpha-PFTs are often expressed from a single operon. Recently, motility-associated killing factor A (MakA), an alpha-PFT, was discovered in Vibrio cholerae. We report that makA is found on the V. cholerae GI-10 genomic island within an operon containing genes for two other potential alpha-PFTs, MakB and MakE. We determined the X-ray crystal structures for MakA, MakB, and MakE and demonstrated that all three are structurally related to the alpha-PFT family in the soluble state, and we modeled their protomer state based on the alpha-PFT AhlB from A. hydrophila. We found that MakA alone is cytotoxic at micromolar concentrations. However, combining MakA with MakB and MakE is cytotoxic at nanomolar concentrations, with specificity for J774 macrophage cells. Our data suggest that MakA, -B, and -E are alpha-PFTs that potentially act as a tripartite pore-forming toxin with specificity for phagocytic cells. IMPORTANCE The bacterium Vibrio cholerae causes gastrointestinal, wound, and skin infections. The motility-associated killing factor A (MakA) was recently shown to be cytotoxic against colon, prostate, and other cancer cells. However, at the outset of this study, the capacity of MakA to damage cells in combination with other Mak proteins encoded in the same operon had not been elucidated. We determined the structures of three Mak proteins and established that they are structurally related to the alpha-PFTs. Compared to MakA alone, the combination of all three toxins was more potent specifically in mouse macrophages. This study highlights the idea that the Mak toxins are selectively cytotoxic and thus may function as a tripartite toxin with cell type specificity. | |||
A Genomic Island of Vibrio cholerae Encodes a Three-Component Cytotoxin with Monomer and Protomer Forms Structurally Similar to Alpha-Pore-Forming Toxins.,Herrera A, Kim Y, Chen J, Jedrzejczak R, Shukla S, Maltseva N, Joachimiak G, Welk L, Wiersum G, Jaroszewski L, Godzik A, Joachimiak A, Satchell KJF J Bacteriol. 2022 May 17;204(5):e0055521. doi: 10.1128/jb.00555-21. Epub 2022 Apr, 18. PMID:35435721<ref>PMID:35435721</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6w08" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Vibch]] | |||
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
[[Category: Endres, M]] | [[Category: Endres, M]] | ||
Revision as of 08:22, 13 July 2022
Crystal Structure of Motility Associated Killing Factor E from Vibrio choleraeCrystal Structure of Motility Associated Killing Factor E from Vibrio cholerae
Structural highlights
Publication Abstract from PubMedAlpha-pore-forming toxins (alpha-PFTs) are secreted by many species of bacteria, including Escherichia coli, Aeromonas hydrophila, and Bacillus thuringiensis, as part of their arsenal of virulence factors, and are often cytotoxic. In particular, for alpha-PFTs, the membrane-spanning channel they form is composed of hydrophobic alpha-helices. These toxins oligomerize at the surface of target cells and transition from a soluble to a protomer state in which they expose their hydrophobic regions and insert into the membrane to form a pore. The pores may be composed of homooligomers of one component or heterooligomers with two or three components, resulting in bi- or tripartite toxins. The multicomponent alpha-PFTs are often expressed from a single operon. Recently, motility-associated killing factor A (MakA), an alpha-PFT, was discovered in Vibrio cholerae. We report that makA is found on the V. cholerae GI-10 genomic island within an operon containing genes for two other potential alpha-PFTs, MakB and MakE. We determined the X-ray crystal structures for MakA, MakB, and MakE and demonstrated that all three are structurally related to the alpha-PFT family in the soluble state, and we modeled their protomer state based on the alpha-PFT AhlB from A. hydrophila. We found that MakA alone is cytotoxic at micromolar concentrations. However, combining MakA with MakB and MakE is cytotoxic at nanomolar concentrations, with specificity for J774 macrophage cells. Our data suggest that MakA, -B, and -E are alpha-PFTs that potentially act as a tripartite pore-forming toxin with specificity for phagocytic cells. IMPORTANCE The bacterium Vibrio cholerae causes gastrointestinal, wound, and skin infections. The motility-associated killing factor A (MakA) was recently shown to be cytotoxic against colon, prostate, and other cancer cells. However, at the outset of this study, the capacity of MakA to damage cells in combination with other Mak proteins encoded in the same operon had not been elucidated. We determined the structures of three Mak proteins and established that they are structurally related to the alpha-PFTs. Compared to MakA alone, the combination of all three toxins was more potent specifically in mouse macrophages. This study highlights the idea that the Mak toxins are selectively cytotoxic and thus may function as a tripartite toxin with cell type specificity. A Genomic Island of Vibrio cholerae Encodes a Three-Component Cytotoxin with Monomer and Protomer Forms Structurally Similar to Alpha-Pore-Forming Toxins.,Herrera A, Kim Y, Chen J, Jedrzejczak R, Shukla S, Maltseva N, Joachimiak G, Welk L, Wiersum G, Jaroszewski L, Godzik A, Joachimiak A, Satchell KJF J Bacteriol. 2022 May 17;204(5):e0055521. doi: 10.1128/jb.00555-21. Epub 2022 Apr, 18. PMID:35435721[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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