A conserved domain of herpes simplex virus ICP34.5 regulates protein phosphatase complex in mammalian cells.
ICP34.5, encoded by herpes simplex virus 1, is a protein phosphatase 1 (PP1) regulatory subunit that mediates dephosphorylation of the alpha subunit of translation initiation factor 2 (eIF2alpha). However, the mechanism of its action remains poorly understood. Here, we show that amino acid substitutions in the arginine-rich motif have differential effects on ICP34.5 activity. The phenotypes parallel with viral protein synthesis and cytopathic effects in virus infected cells. Besides the consensus PP1 binding motif, the Arg-motif appears to enhance the interaction between ICP34.5 and PP1. These results suggest that concerted action between the PP1 binding domain and the effector domain of ICP34.5 is crucial for eIF2alpha dephosphorylation and viral protein synthesis.
Zhang
Cuizhu
C
College of Life Science, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
Tang
Jun
J
Xie
Jia
J
Zhang
Hongkai
H
Li
Yapeng
Y
Zhang
Jie
J
Verpooten
Dustin
D
He
Bin
B
Cao
Youjia
Y
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; D010749:Phosphoprotein Phosphatases