title: Analysis of PKR structure by small-angle scattering.
abstract: Protein kinase R (PKR) is a key component of the interferon antiviral defense pathway. Upon binding double-stranded RNA, PKR undergoes autophosphorylation reactions that activate the kinase. PKR contains an N-terminal double-stranded RNA binding domain, which consists of two tandem double-stranded RNA binding motifs, and a C-terminal kinase domain. We have used small-angle X-ray scattering and small-angle neutron scattering to define the conformation of latent PKR in solution. Guinier analysis indicates a radius of gyration of about 35 A. The p(r) distance distribution function exhibits a peak near 30 A, with a broad shoulder extending to longer distances. Good fits to the scattering data require models that incorporate multiple compact and extended conformations of the two interdomain linker regions. Thus, PKR belongs to the growing family of proteins that contain intrinsically unstructured regions. We propose that the flexible linkers may allow PKR to productively dimerize upon interaction with RNA activators that have diverse structures.
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: VanOudenhove
authors.forename: Eric
authors.initials: E
authors.lastname: Anderson
authors.forename: Susan
authors.initials: S
authors.lastname: Krueger
authors.forename: James L
authors.initials: JL
authors.lastname: Cole
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D007113:Immunity, Innate; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000378:metabolism; D053838:Scattering, Small Angle; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction; D019892:eIF-2 Kinase / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D019892:eIF-2 Kinase