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http://purl.uniprot.org/citations/19015515http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19015515http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19015515http://www.w3.org/2000/01/rdf-schema#comment"The Gram-negative bacterium Vibrio cholerae is the causative agent of a severe diarrheal disease that afflicts three to five million persons annually, causing up to 200,000 deaths. Nearly all V. cholerae strains produce a large multifunctional-autoprocessing RTX toxin (MARTX(Vc)), which contributes significantly to the pathogenesis of cholera in model systems. The actin cross-linking domain (ACD) of MARTX(Vc) directly catalyzes a covalent cross-linking of monomeric G-actin into oligomeric chains and causes cell rounding, but the nature of the cross-linked bond and the mechanism of the actin cytoskeleton disruption remained elusive. To elucidate the mechanism of ACD action and effect on actin, we identified the covalent cross-link bond between actin protomers using limited proteolysis, X-ray crystallography, and mass spectrometry. We report here that ACD catalyzes the formation of an intermolecular iso-peptide bond between residues E270 and K50 located in the hydrophobic and the DNaseI-binding loops of actin, respectively. Mutagenesis studies confirm that no other residues on actin can be cross-linked by ACD both in vitro and in vivo. This cross-linking locks actin protomers into an orientation different from that of F-actin, resulting in strong inhibition of actin polymerization. This report describes a microbial toxin mechanism acting via iso-peptide bond cross-linking between host proteins and is, to the best of our knowledge, the only known example of a peptide linkage between nonterminal glutamate and lysine side chains."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.org/dc/terms/identifier"doi:10.1073/pnas.0808082105"xsd:string
http://purl.uniprot.org/citations/19015515http://purl.org/dc/terms/identifier"doi:10.1073/pnas.0808082105"xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Sawaya M.R."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Sawaya M.R."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Ytterberg A.J."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Ytterberg A.J."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Yeates T.O."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Yeates T.O."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Loo J.A."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Loo J.A."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Loo R.R."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Loo R.R."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Durer Z.A."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Durer Z.A."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Kudryashov D.S."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Kudryashov D.S."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Pashkov I."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Pashkov I."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Prochazkova K."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Prochazkova K."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Reisler E."xsd:string
http://purl.uniprot.org/citations/19015515http://purl.uniprot.org/core/author"Reisler E."xsd:string