Activation of PAK by a bacterial type III effector EspG reveals alternative mechanisms of GTPase pathway regulation

Andrey S. Selyunin, Neal M. Alto

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Small Rho GTPases regulate a diverse range of cellular behavior within a cell. Their ability to function as molecular switches in response to a bound nucleotide state allows them to regulate multiple dynamic processes, including cytoskeleton organization and cellular adhesion. Because the activation of downstream Rho GTPase signaling pathways relies on conserved structural features of target effector proteins (i.e., CRIB domain), these pathways are particularly vulnerable to microbial pathogenic attack. Here, we discuss new findings for how the bacterial virulence factor EspG from EHEC O157:H7 exploits a CRIB-independent activation mechanism of the Rho GTPase effector PAK. We also compare this mechanism to that of EHEC EspFU, a bacterial virulence factor that directly activates N-WASP. While both virulence factors break the inhibitory interaction between the autoinhibitory and activity-bearing domains of PAK or WASP, the underlying mechanics are very distinct from endogenous Cdc42/Rac GTPase regulation. The ability of bacterial proteins to identify novel regulatory principles of host signaling enzymes highlights the multi-level nature of protein activation, and makes them effective tools to study mammalian Rho GTPase signaling pathways.

Original languageEnglish (US)
Pages (from-to)217-221
Number of pages5
JournalSmall GTPases
Volume2
Issue number4
DOIs
StatePublished - Jul 2011

Fingerprint

rho GTP-Binding Proteins
GTP Phosphohydrolases
Virulence Factors
Chemical activation
Enterohemorrhagic Escherichia coli
Bearings (structural)
Bacterial Proteins
Monomeric GTP-Binding Proteins
Mechanics
Cytoskeleton
Proteins
Adhesion
Nucleotides
Switches
Enzymes

Keywords

  • EHEC
  • EPEC
  • EspFU
  • EspG
  • N-WASP
  • PAK
  • Toxin
  • Type III effector
  • WASP

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Activation of PAK by a bacterial type III effector EspG reveals alternative mechanisms of GTPase pathway regulation. / Selyunin, Andrey S.; Alto, Neal M.

In: Small GTPases, Vol. 2, No. 4, 07.2011, p. 217-221.

Research output: Contribution to journalArticle

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