Publikationsdatum:
2009-04-15
Beschreibung:
Pasteurella multocidatoxin is a major virulence factor ofPasteurella 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 Gαq, Gαi, and Gα12/13families by using an as yet unknown mechanism. Here, we show thatPasteurella multocidatoxin deamidates glutamine-205 of Gαi2to glutamic acid. Therefore, the toxin inhibits the intrinsic GTPase activity of Gαiand causes persistent activation of the G protein. A similar modification is also evident for Gαq, but not for the closely related Gα11, which is not a substrate ofPasteurella multocidatoxin. Our data identify the α-subunits of heterotrimeric G proteins as the direct molecular target ofPasteurella multocidatoxin 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.
Print ISSN:
0027-8424
Digitale ISSN:
1091-6490
Thema:
Biologie
,
Medizin
,
Allgemeine Naturwissenschaft
Permalink