Early Australian Optical and Radio Observations of Centaurus A

The discoveries of the radio source Centaurus A and its optical counterpart NGC 5128 were important landmarks in the history of Australian astronomy. NGC 5128 was first observed in August 1826 by James Dunlop during a survey of southern objects at the Parramatta Observatory, west of the settlement at Sydney Cove. The observatory had been founded a few years earlier by Thomas Brisbane, the new governor of the British colony of New South Wales. Just over 120 years later, John Bolton, Gordon Stanley and Bruce Slee discovered the radio source Centaurus A at the Dover Heights field station in Sydney, operated by CSIRO's Radiophysics Laboratory (the forerunner of the Australia Telescope National Facility). This paper will describe this early historical work and summarise further studies of Centaurus A by other Radiophysics groups up to 1960.Comment: 45 pages, 43 figure

A PWWP Domain-Containing Protein Targets the NuA3 Acetyltransferase Complex via Histone H3 Lysine 36 trimethylation to Coordinate Transcriptional Elongation at Coding Regions

Post-translational modifications of histones, such as acetylation and methylation, are differentially positioned in chromatin with respect to gene organization. For example, although histone H3 is often trimethylated on lysine 4 (H3K4me3) and acetylated on lysine 14 (H3K14ac) at active promoter regions, histone H3 lysine 36 trimethylation (H3K36me3) occurs throughout the open reading frames of transcriptionally active genes. The conserved yeast histone acetyltransferase complex, NuA3, specifically binds H3K4me3 through a plant homeodomain (PHD) finger in the Yng1 subunit, and subsequently catalyzes the acetylation of H3K14 through the histone acetyltransferase domain of Sas3, leading to transcription initiation at a subset of genes. We previously found that Ylr455w (Pdp3), an uncharacterized proline-tryptophan-tryptophan-proline (PWWP) domain-containing protein, copurifies with stable members of NuA3. Here, we employ mass-spectrometric analysis of affinity purified Pdp3, biophysical binding assays, and genetic analyses to classify NuA3 into two functionally distinct forms: NuA3a and NuA3b. Although NuA3a uses the PHD finger of Yng1 to interact with H3K4me3 at the 5′-end of open reading frames, NuA3b contains the unique member, Pdp3, which regulates an interaction between NuA3b and H3K36me3 at the transcribed regions of genes through its PWWP domain. We find that deletion of PDP3 decreases NuA3-directed transcription and results in growth defects when combined with transcription elongation mutants, suggesting NuA3b acts as a positive elongation factor. Finally, we determine that NuA3a, but not NuA3b, is synthetically lethal in combination with a deletion of the histone acetyltransferase GCN5, indicating NuA3b has a specialized role at coding regions that is independent of Gcn5 activity. Collectively, these studies define a new form of the NuA3 complex that associates with H3K36me3 to effect transcriptional elongation. MS data are available via ProteomeXchange with identifier PXD001156

Solution-Binding and Molecular Docking Approaches Combine to Provide an Expanded View of Multidrug Recognition in the MDR Gene Regulator BmrR

Solution-binding and molecular docking have been combined with a diverse collection of chemical probes to further elucidate multidrug (MD) recognition in BmrR. Whereas previous efforts have focused on structural elucidations of MD binding, the present study examines features imparted by structure, including the recognition properties of the ligand-pocket, ligand structural requirements, and key factors that define and influence binding. Whereas MD-pockets are generally believed to be featureless and very hydrophobic, log <i>K</i>_Dclog <i>P</i> correlations observed for BmrR and other polyspecific proteins suggest polar contributions are required for broad-spectrum recognition of amphipathic ligands. We show that molecular docking simulations recapitulate key features of MD recognition and have been employed to further inform contributions from structure. In addition to elaborating our understanding of the structures and functional roles of pocket elements that dictate broad-spectrum binding, molecular docking has implication additional features that likely play major roles, including ligand dynamics and multiple ligand-binding modes