Identification of peptide binding sequence of TRIM25 on 14-3-3σ by bioinformatics and biophysical techniques.

14-3-3σ protein is one of the seven isoforms from the highly conserved eukaryotic 14-3-3 protein family. Downregulation of 14-3-3σ expression has been observed in various tumors. TRIM25 is responsible for the proteolytic degradation of 14-3-3σ, in which abrogation of TRIM25 suppressed tumor growth through 14-3-3σ upregulation. However, to date, the exact 14-3-3σ interacting residues of TRIM25 have yet to be resolved. Thus, this study attempts to identify the peptide binding sequence of TRIM25 on 14-3-3σ via both bioinformatics and biophysical techniques. Multiple sequence alignment of the CC domain of TRIM25 revealed five potential peptide binding sequences (Peptide 1-5). Nuclear magnetic resonance (NMR) assay (1H CPMG) identified Peptide 1 as an important sequence for binding to 14-3-3σ. Competition NMR assay suggested that Peptide 1 binds to the amphipathic pocket of 14-3-3σ with an estimated KD of 116.4 µM by isothermal titration calorimetry. Further in silico docking and molecular dynamics simulations studies proposed that Peptide 1 is likely to interact with Lys49, Arg56, Arg129, and Tyr130 residues at the amphipathic pocket of 14-3-3σ. These results suggest that Peptide 1 may serve as a biological probe or a template to design inhibitors of TRIM25-14-3-3σ interaction as a potentially novel class of anticancer agents.Communicated by Ramaswamy H. Sarma.

Dataset of the complete genome of Streptomyces cavourensis strain 2BA6PGT isolated from sediment from the bottom of the salt lake Verkhnee Beloe (Buryatia, Russia).

The Streptomyces cavourensis strain 2BA6PGT was isolated from sediment from the bottom of the salt lake Verkhnee Beloe (Buryatia, Russia). This strain's 7,651,223 bp complete genome has a high G + C content of 72.1% and consists of 7,069 coding sequences and 315 subsystems. The 16S ribosomal RNA of isolate 2BA6PGT was most closely related to Streptomyces cavourensis strain NBRC 13026T (98.91% identity), followed by Streptomyces bacillaris strain ATCC 15855T (95.36%), Streptomyces rhizosphaericola strain 1AS2cT (94.68%), and Streptomyces pluricolorescens strain JCM 4602T (86.75%). These comparisons were supported by pairwise comparisons using average nucleotide identity (ANI) and DNA-DNA hybridization analysis. This is the first complete genome reported on Streptomyces cavourensis isolated from sediment from the bottom of the salt lake Verkhnee Beloe. The complete genome sequence has been deposited at the NCBI GenBank with an accession number CP101140.

The Role of the Z-DNA Binding Domain in Innate Immunity and Stress Granules.

Both DNA and RNA can maintain left-handed double helical Z-conformation under physiological condition, but only when stabilized by Z-DNA binding domain (ZDBD). After initial discovery in RNA editing enzyme ADAR1, ZDBD has also been described in pathogen-sensing proteins ZBP1 and PKZ in host, as well as virulence proteins E3L and ORF112 in viruses. The host-virus antagonism immediately highlights the importance of ZDBD in antiviral innate immunity. Furthermore, Z-RNA binding has been shown to be responsible for the localization of these ZDBD-containing proteins to cytoplasmic stress granules that play central role in coordinating cellular response to stresses. This review sought to consolidate current understanding of Z-RNA sensing in innate immunity and implore possible roles of Z-RNA binding within cytoplasmic stress granules.