Yersinia protein kinase YopO is activated by a novel G-actin binding process.
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Yersinia protein kinase YopO is activated by a novel G-actin binding process. / Trasak, Claudia; Zenner, Gerhardt; Vogel, Annette; Yüksekdag, Gülnihal; Rost, René; Haase, Ilka; Fischer, Markus; Israel, Lars; Imhof, Axel; Linder, Stefan; Schleicher, Michael; Aepfelbacher, Martin.
In: J BIOL CHEM, Vol. 282, No. 4, 4, 2007, p. 2268-2277.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Yersinia protein kinase YopO is activated by a novel G-actin binding process.
AU - Trasak, Claudia
AU - Zenner, Gerhardt
AU - Vogel, Annette
AU - Yüksekdag, Gülnihal
AU - Rost, René
AU - Haase, Ilka
AU - Fischer, Markus
AU - Israel, Lars
AU - Imhof, Axel
AU - Linder, Stefan
AU - Schleicher, Michael
AU - Aepfelbacher, Martin
PY - 2007
Y1 - 2007
N2 - Pathogenic bacteria of the genus Yersinia employ a type III secretion system to inject effector proteins (Yops) into host cells. The Yops down-regulate host cell functions through unique biochemical activities. YopO, a serine/threonine kinase required for Yersinia virulence, is activated by host cell actin via an unknown process. Here we show that YopO kinase is activated by formation of a 1:1 complex with monomeric (G) actin but is unresponsive to filamentous (F) actin. Two separate G-actin binding sites, one in the N-terminal kinase region (amino acids 89-440) and one in the C-terminal guanine nucleotide dissociation inhibitor-like region (amino acids 441-729) of YopO, were identified. Actin binding to both of these sites was necessary for effective autophosphorylation of YopO on amino acids Ser-90 and Ser-95. A S90A/S95A YopO mutant was strongly reduced in substrate phosphorylation, suggesting that autophosphorylation activates YopO kinase activity. In cells the kinase activity of YopO regulated rounding/arborization and was specifically required for inhibition of Yersinia YadA-dependent phagocytosis. Thus, YopO kinase is activated by a novel G-actin binding process, and this appears to be crucial for its anti-host cell functions.
AB - Pathogenic bacteria of the genus Yersinia employ a type III secretion system to inject effector proteins (Yops) into host cells. The Yops down-regulate host cell functions through unique biochemical activities. YopO, a serine/threonine kinase required for Yersinia virulence, is activated by host cell actin via an unknown process. Here we show that YopO kinase is activated by formation of a 1:1 complex with monomeric (G) actin but is unresponsive to filamentous (F) actin. Two separate G-actin binding sites, one in the N-terminal kinase region (amino acids 89-440) and one in the C-terminal guanine nucleotide dissociation inhibitor-like region (amino acids 441-729) of YopO, were identified. Actin binding to both of these sites was necessary for effective autophosphorylation of YopO on amino acids Ser-90 and Ser-95. A S90A/S95A YopO mutant was strongly reduced in substrate phosphorylation, suggesting that autophosphorylation activates YopO kinase activity. In cells the kinase activity of YopO regulated rounding/arborization and was specifically required for inhibition of Yersinia YadA-dependent phagocytosis. Thus, YopO kinase is activated by a novel G-actin binding process, and this appears to be crucial for its anti-host cell functions.
M3 - SCORING: Zeitschriftenaufsatz
VL - 282
SP - 2268
EP - 2277
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 4
M1 - 4
ER -
