6GNN

Exoenzyme T from Pseudomonas aeruginosa in complex with human 14-3-3 protein beta, tetrameric crystal form bound to STO1101

Summary for 6GNN

• Entry DOI: 10.2210/pdb6gnn/pdb
• Descriptor: 14-3-3 protein beta/alpha, Exoenzyme T, 3-(12-oxidanylidene-7-thia-9,11-diazatricyclo[6.4.0.0^{2,6}]dodeca-1(8),2(6),9-trien-10-yl)propanoic acid (3 entities in total)
• Functional Keywords: exot, pseudomonas aeruginosa, adp-ribosylation, nad, toxin
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 55554.55

Authors

Karlberg, T.,Pinto, A.F.,Hornyak, P.,Thorsell, A.G.,Nareoja, K.,Schuler, H. (deposition date: 2018-05-31, release date: 2018-09-26, Last modification date: 2024-01-17)

Primary citation

Karlberg, T.,Hornyak, P.,Pinto, A.F.,Milanova, S.,Ebrahimi, M.,Lindberg, M.,Pullen, N.,Nordstrom, A.,Loverli, E.,Caraballo, R.,Wong, E.V.,Nareoja, K.,Thorsell, A.G.,Elofsson, M.,De La Cruz, E.M.,Bjorkegren, C.,Schuler, H.
14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface.
Nat Commun, 9:3785-3785, 2018

PubMed 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 14-3-3β: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.

PubMed: 30224724
DOI: 10.1038/s41467-018-06194-1

Experimental method

X-RAY DIFFRACTION (3.79 Å)