Pasteurella multocida toxin activates various heterotrimeric G proteins by deamidation

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Joachim H C Orth1, Klaus Aktories

  • 1Institute for Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany. Joachim.Orth@pharmakol.uni-freiburg.de

Toxins
|November 10, 2011
PubMed

Insights

Pasteurella multocida toxin (PMT) activates G proteins by preventing GTP hydrolysis, leading to altered cellular signaling. This study details PMT's molecular mechanism and its impact on cell pathways.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Cellular Biology

Background:

  • Pasteurella multocida toxin (PMT) is a virulence factor that disrupts host cell signaling.
  • PMT targets heterotrimeric G proteins, crucial regulators of cellular processes.

Purpose of the Study:

  • To elucidate the molecular mechanism of PMT action.
  • To analyze the structure-function relationship of PMT.
  • To discuss the impact of PMT on cellular signaling pathways.

Main Methods:

  • Crystal structure analysis of PMT.
  • Investigation of PMT's molecular mode of action.
  • Analysis of cellular signal transduction pathways affected by PMT.

Main Results:

  • PMT deamidates a critical glutamine residue in G protein α-subunits, inhibiting GTP hydrolysis and locking them in an active state.
  • Substrates include Gα(q), Gα(13), and Gα(i)-family proteins.
  • Activated pathways include phospholipase Cβ, Rho-guanine nucleotide exchange factors, and adenylyl cyclase inhibition.

Conclusions:

  • PMT employs a unique mechanism to constitutively activate specific G proteins.
  • Understanding PMT's action provides insights into bacterial pathogenesis and host-pathogen interactions.
  • This knowledge aids in developing strategies to counteract PMT's effects.
Keywords:
G proteinGTPaseGα12/13GαiGαqdeamidationα-subunit

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