3eeb

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<StructureSection load='3eeb' size='340' side='right'caption='[[3eeb]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='3eeb' size='340' side='right'caption='[[3eeb]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3eeb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EEB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3EEB FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3eeb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EEB FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rtxA, vc1451 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 "Bacillo virgola del Koch" Trevisan 1884])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3eeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eeb OCA], [http://pdbe.org/3eeb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eeb RCSB], [http://www.ebi.ac.uk/pdbsum/3eeb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3eeb ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3eeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eeb OCA], [https://pdbe.org/3eeb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eeb RCSB], [https://www.ebi.ac.uk/pdbsum/3eeb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eeb ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MARTX_VIBCH MARTX_VIBCH] Precursor of a multifunctional toxin that causes destruction of the actin cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases when translocated into the host cytoplasm (PubMed:26185092). Upon translocation into the host cell, undergoes autoprocessing in cis mediated by the peptidase C80 domain (also named CPD domain): the protease activity is activated upon binding inositol hexakisphosphate (InsP6) present at the host cell membrane and delivers the Cysteine protease domain-containing toxin F3 chain to the host cytosol (PubMed:17464284, PubMed:18591243, PubMed:18845756, PubMed:19620709, PubMed:19465933). The Cysteine protease domain-containing toxin F3 chain will then further cleave and release effector toxin chains that cause disassembly of the actin cytoskeleton and enhance V.cholerae colonization of the small intestine, possibly by facilitating evasion of phagocytic cells (PubMed:11553575, PubMed:12045243, PubMed:17698573, PubMed:17698571, PubMed:19812690, PubMed:19620709).<ref>PMID:11553575</ref> <ref>PMID:12045243</ref> <ref>PMID:17464284</ref> <ref>PMID:18591243</ref> <ref>PMID:18845756</ref> <ref>PMID:19465933</ref> <ref>PMID:19620709</ref> <ref>PMID:19812690</ref> <ref>PMID:26185092</ref> Following autocatalytic cleavage in cis at the Leu-3441-Ala-3442 site, this chain mediates processing in trans to release other individual toxin chains to the host cytosol (PubMed:19620709). Released effector toxin chains cause disassembly of the actin cytoskeleton and enhance V.cholerae colonization of the small intestine, possibly by facilitating evasion of phagocytic cells (PubMed:17698573, PubMed:17698571).<ref>PMID:17698571</ref> <ref>PMID:17698573</ref> <ref>PMID:19620709</ref> Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin (PubMed:11032799, PubMed:15199181, PubMed:16954226, PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200, PubMed:26228148). Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:23029200).<ref>PMID:11032799</ref> <ref>PMID:15199181</ref> <ref>PMID:16954226</ref> <ref>PMID:17951576</ref> <ref>PMID:19015515</ref> <ref>PMID:19656298</ref> <ref>PMID:23029200</ref> <ref>PMID:26228148</ref> Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin (PubMed:11032799, PubMed:15199181, PubMed:16954226, PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200, PubMed:26228148). Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:23029200).<ref>PMID:11032799</ref> <ref>PMID:15199181</ref> <ref>PMID:16954226</ref> <ref>PMID:17951576</ref> <ref>PMID:19015515</ref> <ref>PMID:19656298</ref> <ref>PMID:23029200</ref> <ref>PMID:26228148</ref> N-epsilon-fatty acyltransferase that mediates lysine-palmitoylation of host Rho GTPase proteins, with a strong preference for host Rac1 (PubMed:29074776). After delivery to the host cytosol, localizes to the host cell membrane where it palmitoylates host Rho GTPase proteins, resulting in loss of all active GTP-bound Rho and subsequent actin depolymerization (PubMed:17474905, PubMed:19434753, PubMed:23184949, PubMed:29074776). Prenylation of host Rac1 at the C-terminus is required for lysine-palmitoylation (PubMed:29074776).<ref>PMID:17474905</ref> <ref>PMID:19434753</ref> <ref>PMID:23184949</ref> <ref>PMID:29074776</ref> Indirectly activates the small GTPase CDC42.<ref>PMID:25427654</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3eeb ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3eeb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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Vibrio cholerae RTX (repeats in toxin) is an actin-disrupting toxin that is autoprocessed by an internal cysteine protease domain (CPD). The RTX CPD is efficiently activated by the eukaryote-specific small molecule inositol hexakisphosphate (InsP6), and we present the 2.1 angstrom structure of the RTX CPD in complex with InsP6. InsP6 binds to a conserved basic cleft that is distant from the protease active site. Biochemical and kinetic analyses of CPD mutants indicate that InsP6 binding induces an allosteric switch that leads to the autoprocessing and intracellular release of toxin-effector domains.
 
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Small molecule-induced allosteric activation of the Vibrio cholerae RTX cysteine protease domain.,Lupardus PJ, Shen A, Bogyo M, Garcia KC Science. 2008 Oct 10;322(5899):265-8. PMID:18845756<ref>PMID:18845756</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 3eeb" style="background-color:#fffaf0;"></div>
 
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillo virgola del koch trevisan 1884]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Bogyo, M]]
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[[Category: Vibrio cholerae]]
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[[Category: Garcia, K C]]
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[[Category: Bogyo M]]
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[[Category: Lupardus, P J]]
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[[Category: Garcia KC]]
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[[Category: Shen, A]]
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[[Category: Lupardus PJ]]
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[[Category: Cysteine protease]]
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[[Category: Shen A]]
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[[Category: Inositol hexakisphosphate]]
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[[Category: Martx]]
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[[Category: Repeats-in-toxin]]
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[[Category: Rtx]]
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[[Category: Toxin]]
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[[Category: V. cholerae]]
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Current revision

Structure of the V. cholerae RTX cysteine protease domain

PDB ID 3eeb

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Proteopedia Page Contributors and Editors (what is this?)

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