14-3-3 Activated Bacterial Exotoxins AexT and ExoT Share Actin and the SH2 Domains of CRK Proteins as Targets for ADP-Ribosylation
Ebenwaldner, Carmen LU ; Hornyak, Peter ; García-Saura, Antonio Ginés LU ; Torretta, Archimede LU ; Anoosheh, Saber ; Hofer, Anders and Schüler, Herwig LU
(2022)
In Pathogens
11(12).
- Abstract
Bacterial exotoxins with ADP-ribosyltransferase activity can be divided into distinct clades based on their domain organization. Exotoxins from several clades are known to modify actin at Arg177; but of the 14-3-3 dependent exotoxins only Aeromonas salmonicida exoenzyme T (AexT) has been reported to ADP-ribosylate actin. Given the extensive similarity among the 14-3-3 dependent exotoxins, we initiated a structural and biochemical comparison of these proteins. Structural modeling of AexT indicated a target binding site that shared homology with Pseudomonas aeruginosa Exoenzyme T (ExoT) but not with Exoenzyme S (ExoS). Biochemical analyses confirmed that the catalytic activities of both exotoxins were stimulated by agmatine, indicating... (More)
Bacterial exotoxins with ADP-ribosyltransferase activity can be divided into distinct clades based on their domain organization. Exotoxins from several clades are known to modify actin at Arg177; but of the 14-3-3 dependent exotoxins only Aeromonas salmonicida exoenzyme T (AexT) has been reported to ADP-ribosylate actin. Given the extensive similarity among the 14-3-3 dependent exotoxins, we initiated a structural and biochemical comparison of these proteins. Structural modeling of AexT indicated a target binding site that shared homology with Pseudomonas aeruginosa Exoenzyme T (ExoT) but not with Exoenzyme S (ExoS). Biochemical analyses confirmed that the catalytic activities of both exotoxins were stimulated by agmatine, indicating that they ADP-ribosylate arginine residues in their targets. Side-by-side comparison of target protein modification showed that AexT had activity toward the SH2 domain of the Crk-like protein (CRKL), a known target for ExoT. We found that both AexT and ExoT ADP-ribosylated actin and in both cases, the modification compromised actin polymerization. Our results indicate that AexT and ExoT are functional homologs that affect cytoskeletal integrity via actin and signaling pathways to the cytoskeleton.
(Less)
- author
- Ebenwaldner, Carmen
LU
; Hornyak, Peter
; García-Saura, Antonio Ginés
LU
; Torretta, Archimede
LU
; Anoosheh, Saber
; Hofer, Anders
and Schüler, Herwig
LU
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 14-3-3 activated bacterial exotoxins, actin, ADP-ribosylation, Aeromonas salmonicid, protein refolding, Pseudomonas aeruginosa, type III secretion system
- in
- Pathogens
- volume
- 11
- issue
- 12
- article number
- 1497
- publisher
- MDPI AG
- external identifiers
-
- pmid:36558830
- scopus:85144683837
- ISSN
- 2076-0817
- DOI
- 10.3390/pathogens11121497
- language
- English
- LU publication?
- yes
- id
- a3bbc894-2621-48b6-a7e5-91709833c67e
- date added to LUP
- 2023-01-05 12:16:57
- date last changed
- 2024-06-28 00:11:40
@article{a3bbc894-2621-48b6-a7e5-91709833c67e,
abstract = {{<p>Bacterial exotoxins with ADP-ribosyltransferase activity can be divided into distinct clades based on their domain organization. Exotoxins from several clades are known to modify actin at Arg177; but of the 14-3-3 dependent exotoxins only Aeromonas salmonicida exoenzyme T (AexT) has been reported to ADP-ribosylate actin. Given the extensive similarity among the 14-3-3 dependent exotoxins, we initiated a structural and biochemical comparison of these proteins. Structural modeling of AexT indicated a target binding site that shared homology with Pseudomonas aeruginosa Exoenzyme T (ExoT) but not with Exoenzyme S (ExoS). Biochemical analyses confirmed that the catalytic activities of both exotoxins were stimulated by agmatine, indicating that they ADP-ribosylate arginine residues in their targets. Side-by-side comparison of target protein modification showed that AexT had activity toward the SH2 domain of the Crk-like protein (CRKL), a known target for ExoT. We found that both AexT and ExoT ADP-ribosylated actin and in both cases, the modification compromised actin polymerization. Our results indicate that AexT and ExoT are functional homologs that affect cytoskeletal integrity via actin and signaling pathways to the cytoskeleton.</p>}},
author = {{Ebenwaldner, Carmen and Hornyak, Peter and García-Saura, Antonio Ginés and Torretta, Archimede and Anoosheh, Saber and Hofer, Anders and Schüler, Herwig}},
issn = {{2076-0817}},
keywords = {{14-3-3 activated bacterial exotoxins; actin; ADP-ribosylation; Aeromonas salmonicid; protein refolding; Pseudomonas aeruginosa; type III secretion system}},
language = {{eng}},
number = {{12}},
publisher = {{MDPI AG}},
series = {{Pathogens}},
title = {{14-3-3 Activated Bacterial Exotoxins AexT and ExoT Share Actin and the SH2 Domains of CRK Proteins as Targets for ADP-Ribosylation}},
url = {{http://dx.doi.org/10.3390/pathogens11121497}},
doi = {{10.3390/pathogens11121497}},
volume = {{11}},
year = {{2022}},
}