14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface.
Nat Commun
; 9(1): 3785, 2018 09 17.
Article
em En
| MEDLINE
| ID: mdl-30224724
ABSTRACT
Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3ßExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.
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Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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ADP Ribose Transferases
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Proteínas Ativadoras de GTPase
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Proteínas 14-3-3
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article