How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat Struct Biol 2001 Jan;8(1):23-6
Date
01/03/2001Pubmed ID
11135665DOI
10.1038/83007Scopus ID
2-s2.0-0035171524 (requires institutional sign-in at Scopus site) 96 CitationsAbstract
Pseudomonas aeruginosa is an opportunistic bacterial pathogen. One of its major toxins, ExoS, is translocated into eukaryotic cells by a type III secretion pathway. ExoS is a dual function enzyme that affects two different Ras-related GTP binding proteins. The C-terminus inactivates Ras through ADP ribosylation, while the N-terminus inactivates Rho proteins through its GTPase activating protein (GAP) activity. Here we have determined the three-dimensional structure of a complex between Rac and the GAP domain of ExoS in the presence of GDP and AlF3. Composed of approximately 130 residues, this ExoS domain is the smallest GAP hitherto described. The GAP domain of ExoS is an all-helical protein with no obvious structural homology, and thus no recognizable evolutionary relationship, with the eukaryotic RhoGAP or RasGAP fold. Similar to other GAPs, ExoS downregulates Rac using an arginine finger to stabilize the transition state of the GTPase reaction, but the details of the ExoS-Rac interaction are unique. Considering the intrinsic resistance of P. aeruginosa to antibiotics, this might open up a new avenue towards blocking its pathogenicity.
Author List
Würtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer AAuthor
Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Aluminum CompoundsAmino Acid Sequence
Bacterial Toxins
Binding Sites
Catalysis
Crystallography, X-Ray
Down-Regulation
Fluorides
GTPase-Activating Proteins
Guanosine Diphosphate
Histidine Kinase
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Folding
Protein Kinases
Protein Structure, Secondary
Protein Structure, Tertiary
Pseudomonas aeruginosa
Sequence Alignment
Structure-Activity Relationship
rac GTP-Binding Proteins