PROSITE documentation PDOC52059Bacterial Rho GTPase-activating protein (GAP) domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC52059
Manipulation of the actin cytoskeleton in eukaryotic cells is one of the principal virulence strategies used by bacterial pathogens. Because they are master regulators of actin cytoskeleton dynamics, the Rho family of small GTPases are frequent targets for bacterial cytotoxins. Like other G proteins, Rho GTPases are molecular switches that are controlled through nucleotide exchange and are active in the GTP form and inactive in the GDP form. Nucleotide exchange is regulated by guanine nucleotide exchange factors, which activate Rho by stimulating the exchange of GDP for GTP, and by GAPs, which inactivate Rho by stimulating the hydrolysis of the γ-phosphate of GTP, yielding Rho-GDP. The following bacterial cytotoxins contain a domain which acts as a GAP for various Rho GTPases [1,2,3]:
- Yersinia pestis cytotoxic effector YopE.
- Pseudomonas aeruginosa ExoS and ExoT are bifunctional toxins: their N- terminal domain is a RhoGAP, and their C-terminal domain inactivates Ras by ADP ribosylation (see <PDOC51996>).
- Salmonella enterica SptP is a modular protein consisting of three distinct domains: a chaperone-binding domain, a GAP domain, and a tyrosine phosphatase domain (see <PDOC00323>).
The structure of the ~130-residue bacterial RhoGAP domain is almost completely helical; the only nonhelical portion is a small two-stranded β-sheet connected by a tight turn (see <PDB:1HE1>). Its main building block is a right-handed antiparallel four-helix bundle with a characteristic up-down-up-down topology. The N- and C-termini are located on one side of the bundle, whereas the other side is capped by irregular additional helices. Like their eukaryotic counterparts, the bacterial RhoGAPs use a conserved arginine side-chain to catalyze GTP hydrolysis [1,2,3].
The profile we developed covers the entire bacterial RhoGAP domain.
Last update:March 2025 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
1 | Authors | Stebbins C.E. Galan J.E. |
Title | Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. | |
Source | Mol. Cell. 6:1449-1460(2000). | |
PubMed ID | 11163217 | |
DOI | 10.1016/s1097-2765(00)00141-6 |
2 | Authors | Wuertele M. Wolf E. Pederson K.J. Buchwald G. Ahmadian M.R. Barbieri J.T. Wittinghofer A. |
Title | How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. | |
Source | Nat. Struct. Biol. 8:23-26(2001). | |
PubMed ID | 11135665 | |
DOI | 10.1038/83007 |
3 | Authors | Evdokimov A.G. Tropea J.E. Routzahn K.M. Waugh D.S. |
Title | Crystal structure of the Yersinia pestis GTPase activator YopE. | |
Source | Protein. Sci. 11:401-408(2002). | |
PubMed ID | 11790850 | |
DOI | 10.1110/ps.34102 |
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