PKR and eIF2α: Integration of Kinase Dimerization, Activation, and Substrate Docking
نویسندگان
چکیده
The antiviral RNA-dependent protein kinase, PKR, binds to viral double-stranded RNA in the cell and halts protein synthesis by phosphorylating the alpha subunit of the translation initiation factor eIF2. In this issue of Cell, two complementary papers Dar et al. (2005) and Dey et al. (2005) address the interaction between PKR and eIF2alpha. The structures of eIF2alpha bound to PKR reveal that PKR forms a dimer, the interface of which is essential for kinase activation, and demonstrate how this protein substrate docks to its kinase. The structures, coupled with mutagenesis analysis, also demonstrate how phosphorylation of the activation loop can allosterically couple two distal regions, the dimerization and substrate recognition interfaces.
منابع مشابه
Mechanistic Link between PKR Dimerization, Autophosphorylation, and eIF2α Substrate Recognition
The antiviral protein kinase PKR inhibits protein synthesis by phosphorylating the translation initiation factor eIF2alpha on Ser51. Binding of double-stranded RNA to the regulatory domains of PKR promotes dimerization, autophosphorylation, and the functional activation of the kinase. Herein, we identify mutations that activate PKR in the absence of its regulatory domains and map the mutations ...
متن کاملHigher-Order Substrate Recognition of eIF2α by the RNA-Dependent Protein Kinase PKR
In response to binding viral double-stranded RNA byproducts within a cell, the RNA-dependent protein kinase PKR phosphorylates the alpha subunit of the translation initiation factor eIF2 on a regulatory site, Ser51. This triggers the general shutdown of protein synthesis and inhibition of viral propagation. To understand the basis for substrate recognition by and the regulation of PKR, we deter...
متن کاملViral Evolved Inhibition Mechanism of the RNA Dependent Protein Kinase PKR's Kinase Domain, a Structural Perspective
The protein kinase PKR activated by viral dsRNA, phosphorylates the eIF2α, which inhibit the mechanism of translation initiation. Viral evolved proteins mimicking the eIF2α block its phosphorylation and help in the viral replication. To decipher the molecular basis for the PKR's substrate and inhibitor interaction mechanisms, we carried the molecular dynamics studies on the catalytic domain of ...
متن کاملCellular SRC kinases and dsRNA dependent protein kinase (PKR) play key role in intracellular viral (CVB3) replication
SRC kinases and PKR are intracellular protein kinases, which play key roles in intracellular viral replication. In this research, the effect of SRC kinase inhibition and PKR activation and inhibition on replication of coxsakievirus (CVB3), an entrovirus of the family picornaviridae – causative agents of fatal myocarditis, was studied. Vero and Hela cells were cultured and infected with CVB3 in ...
متن کاملCellular SRC kinases and dsRNA dependent protein kinase (PKR) play key role in intracellular viral (CVB3) replication
SRC kinases and PKR are intracellular protein kinases, which play key roles in intracellular viral replication. In this research, the effect of SRC kinase inhibition and PKR activation and inhibition on replication of coxsakievirus (CVB3), an entrovirus of the family picornaviridae – causative agents of fatal myocarditis, was studied. Vero and Hela cells were cultured and infected with CVB3 in ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cell
دوره 122 شماره
صفحات -
تاریخ انتشار 2005