ArticleBiochemistry2008
Domain stabilities in protein kinase R (PKR): evidence for weak interdomain interactions.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Contribution of dsRBD2 to PKR Activation.ACS omega · 2021Article
- VHS, US3 and UL13 viral tegument proteins are required for Herpes Simplex Virus-Induced modification of protein kinase R.Scientific reports · 2020Article
- The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators.RNA (New York, N.Y.) · 2019Review
- Interaction of PKR with single-stranded RNA.Scientific reports · 2017Article
- Role of the Interdomain Linker in RNA-Activated Protein Kinase Activation.Biochemistry · 2016Article
- The Regulatory and Kinase Domains but Not the Interdomain Linker Determine Human Double-stranded RNA-activated Kinase (PKR) Sensitivity to Inhibition by Viral Non-coding RNAs.The Journal of biological chemistry · 2015Article
- Regulation of PKR by RNA: formation of active and inactive dimers.Biochemistry · 2015Article
- Article
- Monitoring activation of the antiviral pattern recognition receptors RIG-I and PKR by limited protease digestion and native PAGE.Journal of visualized experiments : JoVE · 2014Article
- Domain interactions in adenovirus VAI RNA mediate high-affinity PKR binding.Journal of molecular biology · 2014Article
- The eIF2α kinases: their structures and functions.Cellular and molecular life sciences : CMLS · 2013Review
- Improved control of tuberculosis and activation of macrophages in mice lacking protein kinase R.PloS one · 2012Article
- Heparin activates PKR by inducing dimerization.Journal of molecular biology · 2011Article
- Allosteric activation mechanism of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknB.Structure (London, England : 1993) · 2010Article
- Analysis of monomeric and dimeric phosphorylated forms of protein kinase R.Biochemistry · 2010Article
- Analysis of PKR structure by small-angle scattering.Journal of molecular biology · 2009Article
- Mechanism of PKR Activation by dsRNA.Journal of molecular biology · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
PKR (protein kinase R) is induced by interferon and is a key component of the innate immunity antiviral pathway. Upon binding dsRNA, PKR undergoes autophosphorylation reactions that activate the kinase, leading it to phosphorylate eIF2alpha, thus inhibiting protein synthesis in virally infected cells. PKR contains a dsRNA-binding domain (dsRBD) and a kinase domain. The dsRBD is composed of two tandem dsRNA-binding motifs. An autoinhibition model for PKR has been proposed, whereby dsRNA binding activates the enzyme by inducing a conformational change that relieves the latent enzyme of the inhibition that is mediated by the interaction of the dsRBD with the kinase. However, recent biophysical data support an open conformation for the latent enzyme, where activation is mediated by dimerization of PKR induced upon binding dsRNA. We have probed the importance of interdomain contacts by comparing the relative stabilities of isolated domains with the same domain in the context of the intact enzyme using equilibrium chemical denaturation experiments. The two dsRNA-binding motifs fold independently, with the C-terminal motif exhibiting greater stability. The kinase domain is stabilized by about 1.5 kcal/mol in the context of the holenzyme, and we detect low-affinity binding of the kinase and dsRBD constructs in solution, indicating that these domains interact weakly. Limited proteolysis measurements confirm the expected domain boundaries and reveal that the activation loop in the kinase is accessible to cleavage and unstructured. Autophosphorylation induces a conformation change that blocks proteolysis of the activation loop.
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