2024年9月18日 · Protein kinase R (PKR) functions in the eukaryotic innate immune system as a first-line defense against viral infections. PKR binds viral dsRNA, leading to autophosphorylation and activation. In its active state, PKR can phosphorylate its primary substrate, eIF2α, which blocks the initiation of translation in the infected cell.

Model for PKR activation. PKR exists in an open conformation (i) in a weak monomer-dimer equilibrium. Dimerization is induced by binding to dsRNA (ii) or at high protein concentration (iii), producing an enzyme form competent to undergo autophosphorylation. ATP is able to bind readily to both monomeric and dimeric PKR.

2016年6月16日 · PKR是一个551个氨基酸残基组成的蛋白激酶，由两个功能部分组成，一个N末端的 RNA结合结构域和一个C末端的激酶结构域，这两个结构域之间通过一个80个氨基酸残

Here we review the role of PKR as an eIF2α kinase, its participation in the regulation of the NF-κB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV). PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2.

Here we report that PKR activation by PACT causes cellular apoptosis in addition to PKR autophosphorylation and translation inhibition. We analyzed the structure-function relationship of PACT by measuring its ability to bind and activate PKR in vitro and in vivo.

2005年1月7日 · We propose a chain reaction model for PKR dsRNA-independent activation where dimerization of latent enzyme followed by intermolecular phosphorylation serves as the initiation step. Subsequent propagation steps likely involve phosphorylation of latent PKR monomers by activated enzyme within high-affinity heterodimers.

RNA-generated phosphorylated PKR (PKR TAR-P) was made by incubating wild-type full-length human PKR (1 μ m) and HIV TAR RNA in the presence of ATP (1 m m) and MgCl 2 (2 m m) at 30 °C for 2 h in a buffered solution containing Tris·HCl (pH 7.5), 100 m m NaCl, and 5 m m β-mercaptoethanol and purified as described above.

2017年8月1日 · A few ATP competitive inhibitors of the PKR have been reported in the literature with promising results in vitro and in vivo. The aim of this study was to unravel the structural interactions between these inhibitors and the PKR kinase …

2007年2月1日 · The double-stranded (ds) RNA-activated protein kinase, PKR, has a key role in the innate immunity response to viral infection in higher eukaryotes. PKR contains an N-terminal dsRNA-binding domain and a C-terminal kinase domain.

2011年2月2日 · Biochemical and computational studies show that palmitate binds to PKR, near the ATP-binding site, thereby inhibiting its autophosphorylation at Thr451 and Thr446. Mutation studies suggests that Lys296 and Asp432 in the ATP binding site on the PKR protein are important for palmitate binding.