Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06194-1
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Funding
- Swedish Foundation for Strategic Research [SB12-0022]
- Swedish Research Council [2012-2802, 2015-4200, 2015-4603]
- IngaBritt and Arne Lundbergs Research Foundation [403, 2015-089]
- National Institutes of Health (R01 Grant) [GM097348]
- National Science Foundation Graduate Research Fellowship [DGE-1122492]
- Wenner-Gren Foundation fellowship
- Swedish Foundation for Strategic Research (SSF) [SB12-0022] Funding Source: Swedish Foundation for Strategic Research (SSF)
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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 14-3-3 beta: ExoS 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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