Structural Requirements for Yersinia YopJ Inhibition of MAP Kinase Pathways

被引:24
作者
Hao, Yi-Heng [1 ]
Wang, Yong [3 ]
Burdette, Dara [1 ]
Mukherjee, Sohini [1 ]
Keitany, Gladys [4 ]
Goldsmith, Elizabeth [2 ]
Orth, Kim [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX USA
[3] Arizona State Univ, Sch Life Sci, Tempe, AZ USA
[4] Univ Washington, Sch Pub Hlth, Seattle, WA USA
来源
PLOS ONE | 2008年 / 3卷 / 01期
关键词
D O I
10.1371/journal.pone.0001375
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MAPK signaling cascades are evolutionally conserved. The bacterial effector, YopJ, uses the unique activity of Ser/Thr acetylation to inhibit the activation of the MAPK kinase (MKK) and prevent activation by phosphorylation. YopJ is also able to block yeast MAPK signaling pathways using this mechanism. Based on these observations, we performed a genetic screen to isolate mutants in the yeast MKK, Pbs2, that suppress YopJ inhibition. One suppressor contains a mutation in a conserved tyrosine residue and bypasses YopJ inhibition by increasing the basal activity of Pbs2. Mutations on the hydrophobic face of the conserved G alpha-helix in the kinase domain prevent both binding and acetylation by YopJ. Corresponding mutants in human MKKs showed that they are conserved not only structurally, but also functionally. These studies reveal a conserved binding site found on the superfamily of MAPK kinases while providing insight into the molecular interactions required for YopJ inhibition.
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页数:9
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