Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 105 (2008-11-25), Heft 47, S. 18537-18542
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Zugriff:
The Gram-negative bacterium Vibrio cholera 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 MARTXVC 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 DNasel-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 [ABSTRACT FROM AUTHOR]
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Titel: |
Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin.
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Autor/in / Beteiligte Person: | Kudryashov, Dmitri S. ; Oztug Durer, Zeynep A. ; Ytterberg, A. Jimmy ; Sawaya, Michael R. ; Pashkov, Inna ; Prochazkova, Katerina ; Yeates, Todd O. ; Ogorzalek Loo, Rachel R. ; Loo, Joseph A. ; Fuliner Satchell, Karla J. ; Reisler, Emil |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 105 (2008-11-25), Heft 47, S. 18537-18542 |
Veröffentlichung: | 2008 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.0808082105 |
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