Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation

Joachim H C Orth, Inga Preuss, Ines Fester, Andreas Schlosser, Brenda A. Wilson, Klaus Aktories

Research output: Contribution to journalArticlepeer-review

Abstract

Pasteurella multocida toxin is a major virulence factor of Pasteu-rella multocida, which causes pasteurellosis in men and animals and atrophic rhinitis in rabbits and pigs. The ≈145 kDa protein toxin stimulates various signal transduction pathways by activating heterotrimeric G proteins of the Gα q, Gα q and Gα 12/13 families by using an as yet unknown mechanism. Here, we show that Pasteurella multocida toxin deamidates glutamine-205 of Gα i2 to glutamic acid. Therefore, the toxin inhibits the intrinsic GTPase activity of Gα i; and causes persistent activation of the G protein. A similar modification is also evident for Gα q, but not for the closely related Gα 11, which is not a substrate of Pasteurella multocida toxin. Our data identify the α-subunits of heterotrimeric G proteins as the direct molecular target of Pasteurella multocida toxin and indicate that the toxin does not act like a protease, which was suggested from its thiol protease-like catalytic triad, but instead causes constitutive activation of G proteins by deamidase activity.

Original languageEnglish (US)
Pages (from-to)7179-7184
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number17
DOIs
StatePublished - Apr 28 2009

Keywords

  • Bacterial protein toxin
  • Gi protein
  • Posttranslational modification
  • Transglutaminase

ASJC Scopus subject areas

  • General

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