{PDOC52059}
{PS52059; BACT_RHOGAP}
{BEGIN}
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* Bacterial Rho GTPase-activating protein (GAP) domain profile *
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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 gamma-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 beta-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: March 2025 / First entry.

[ 1] Stebbins C.E., Galan J.E.
     "Modulation of host signaling by a bacterial mimic: structure of the
     Salmonella  effector SptP bound to Rac1."
     Mol. Cell. 6:1449-1460(2000).
     PubMed=11163217; DOI=10.1016/s1097-2765(00)00141-6
[ 2] Wuertele M., Wolf E., Pederson K.J., Buchwald G., Ahmadian M.R.,
     Barbieri J.T., Wittinghofer A.
     "How the Pseudomonas aeruginosa ExoS toxin downregulates Rac."
     Nat. Struct. Biol. 8:23-26(2001).
     PubMed=11135665; DOI=10.1038/83007
[ 3] Evdokimov A.G., Tropea J.E., Routzahn K.M., Waugh D.S.
     "Crystal structure of the Yersinia pestis GTPase activator YopE."
     Protein. Sci. 11:401-408(2002).
     PubMed=11790850; DOI=10.1110/ps.34102

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