Structure and function of SARS-CoV-2 polymerase

Coronaviruses use an RNA-dependent RNA polymerase (RdRp) to replicate and express their genome. The RdRp associates with additional non-structural proteins (nsps) to form a replication–transcription complex (RTC) that carries out RNA synthesis, capping and proofreading. However, the structure of the RdRp long remained elusive, thus limiting our understanding of coronavirus genome expression and replication. Recently, the cryo-electron microscopy structure of SARS-CoV-1 RdRp was reported. Driven by the ongoing COVID-19 pandemic, structural data on the SARS-CoV-2 polymerase and associated factors has since emerged at an unprecedented pace, with more than twenty structures released to date. This review provides an overview of the currently available coronavirus RdRp structures and outlines how they have, together with functional studies, led to a molecular understanding of the viral polymerase, its interactions with accessory factors and the mechanisms by which promising antivirals may inhibit coronavirus replication

Structural and mechanistic basis of RNA processing by protein-only ribonuclease P enzymes

Ribonuclease P (RNase P) enzymes are responsible for the 5′ processing of tRNA precursors. In addition to the well-characterised ribozyme-based RNase P enzymes, an evolutionarily distinct group of protein-only RNase Ps exists. These proteinaceous RNase Ps (PRORPs) can be found in all three domains of life and can be divided into two structurally different types: eukaryotic and pro- karyotic. Recent structural studies on members of both families reveal a surpris- ing diversity of molecular architectures, but also highlight conceptual and mechanistic similarities. Here, we provide a comparison between the different types of PRORP enzymes and review how the combination of structural, bio- chemical, and biophysical studies has led to a molecular picture of protein- mediated tRNA processing

The perturbed sublimation rim of the dust disk around the post-AGB binary IRAS08544-4431

Context: Post-Asymptotic Giant Branch (AGB) binaries are surrounded by stable dusty and gaseous disks similar to the ones around young stellar objects. Whereas significant effort is spent on modeling observations of disks around young stellar objects, the disks around post-AGB binaries receive significantly less attention, even though they pose significant constraints on theories of disk physics and binary evolution. Aims: We want to examine the structure of and phenomena at play in circumbinary disks around post-AGB stars. We continue the analysis of our near-infrared interferometric image of the inner rim of the circumbinary disk around IRAS08544-4431. We want to understand the physics governing this inner disk rim. Methods: We use a radiative transfer model of a dusty disk to reproduce simultaneously the photometry as well as the near-infrared interferometric dataset on IRAS08544-4431. The model assumes hydrostatic equilibrium and takes dust settling self-consistently into account. Results: The best-fit radiative transfer model shows excellent agreement with the spectral energy distribution up to mm wavelengths as well as with the PIONIER visibility data. It requires a rounded inner rim structure, starting at a radius of 8.25 au. However, the model does not fully reproduce the detected over-resolved flux nor the azimuthal flux distribution of the inner rim. While the asymmetric inner disk rim structure is likely to be the consequence of disk-binary interactions, the origin of the additional over-resolved flux remains unclear. Conclusions: As in young stellar objects, the disk inner rim of IRAS08544-4431 is ruled by dust sublimation physics. Additional observations are needed to understand the origin of the extended flux and the azimuthal perturbation at the inner rim of the disk.Comment: Accepted for publication in A&A, 13 figures, 13 page

The evolved circumbinary disk of AC Her: a radiative transfer, interferometric and mineralogical study

We aim to constrain the structure of the circumstellar material around the post-AGB binary and RV Tauri pulsator AC Her. We want to constrain the spatial distribution of the amorphous as well as of the crystalline dust. We present very high-quality mid-IR interferometric data that were obtained with MIDI/VLTI. We analyse the MIDI data and the full SED, using the MCMax radiative transfer code, to find a good structure model of AC Her's circumbinary disk. We include a grain size distribution and midplane settling of dust self-consistently. The spatial distribution of crystalline forsterite in the disk is investigated with the mid-IR features, the 69~$\mu$m band and the 11.3~$\mu$m signatures in the interferometric data. All the data are well fitted. The inclination and position angle of the disk are well determined at i=50+-8 and PA=305+-10. We firmly establish that the inner disk radius is about an order of magnitude larger than the dust sublimation radius. Significant grain growth has occurred, with mm-sized grains being settled to the midplane of the disk. A large dust mass is needed to fit the sub-mm fluxes. By assuming {\alpha}=0.01, a good fit is obtained with a small grain size power law index of 3.25, combined with a small gas/dust ratio <10. The resulting gas mass is compatible with recent estimates employing direct gas diagnostics. The spatial distribution of the forsterite is different from the amorphous dust, as more warm forsterite is needed in the surface layers of the inner disk. The disk in AC Her is very evolved, with its small gas/dust ratio and large inner hole. Mid-IR interferometry offers unique constraints, complementary to mid-IR features, for studying the mineralogy in disks. A better uv coverage is needed to constrain in detail the distribution of the crystalline forsterite in AC Her, but we find strong similarities with the protoplanetary disk HD100546.Comment: update with final version published in A&

Hierarchical folding of the catalytic core during mitochondrial ribosome biogenesis

Final maturation steps during ribosome biogenesis require the assistance of assembly and quality control factors to ensure the folding of rRNA and proteins into a functional translation machinery. Here we integrate several recent structural snapshots of native large ribosomal subunit intermediates into the complex pathway of mitochondrial ribosome assembly

Absolute dimensions of solar-type eclipsing binaries. EF Aquarii: a G0 test for stellar evolution models

Recent studies have shown that stellar chromospheric activity, and its effect on convective energy transport in the envelope, is most likely the cause of significant radius and temperature discrepancies between theoretical evolution models and observations. We aim to determine absolute dimensions and abundances for the solar-type detached eclipsing binary EF Aqr, and to perform a detailed comparison with results from recent stellar evolutionary models. uvby-beta standard photometry was obtained with the Stromgren Automatic Telescope. The broadening function formalism was applied on spectra observed with HERMES at the Mercator telescope in La Palma, to obtain radial velocity curves. Masses and radii with a precision of 0.6% and 1.0% respectively have been established for both components of EF Aqr. The active 0.956 M_sol secondary shows star spots and strong Ca II H and K emission lines. The 1.224 M_sol primary shows signs of activity as well, but at a lower level. An [Fe/H] abundance of 0.00+-0.10 is derived with similar abundances for Si, Ca, Sc, Ti, V, Cr, Co, and Ni. Solar calibrated evolutionary models such as Yonsei-Yale, Victoria-Regina and BaSTI isochrones and evolutionary tracks are unable to reproduce EF Aqr, especially for the secondary, which is 9% larger and 400 K cooler than predicted. Models adopting significantly lower mixing length parameters l/H_p remove these discrepancies, as seen in other solar type binaries. For the observed metallicity, Granada models with a mixing length of l/H_p=1.30 (primary) and 1.05 (secondary) reproduce both components at a common age of 1.5+-0.6 Gyr. Observations of EF Aqr suggests that magnetic activity, and its effect on envelope convection, is likely to be the cause of discrepancies in both radius and temperature, which can be removed by adjusting the mixing length parameter of the models downwards.Comment: 11 pages, 8 figures, accepted for publication by A&

Structural basis of RNA processing by human mitochondrial RNase P

Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry out RNA cleavage and methylation by unknown mechanisms. Here, we present the cryo-EM structure of human mtRNase P bound to precursor tRNA, which reveals a unique mechanism of substrate recognition and processing. Subunits TRMT10C and SDR5C1 form a subcomplex that binds conserved mitochondrial tRNA elements, including the anticodon loop, and positions the tRNA for methylation. The endonuclease PRORP is recruited and activated through interactions with its PPR and nuclease domains to ensure precise pre-tRNA cleavage. The structure provides the molecular basis for the first step of RNA processing in human mitochondria

Imaging the dust sublimation front of a circumbinary disk

We present the first near-IR milli-arcsecond-scale image of a post-AGB binary that is surrounded by hot circumbinary dust. A very rich interferometric data set in six spectral channels was acquired of IRAS08544-4431 with the new RAPID camera on the PIONIER beam combiner at the Very Large Telescope Interferometer (VLTI). A broadband image in the \textit{H} band was reconstructed by combining the data of all spectral channels using the SPARCO method. We spatially separate all the building blocks of the IRAS08544-4431 system in our milliarcsecond-resolution image. Our dissection reveals a dust sublimation front that is strikingly similar to that expected in early-stage protoplanetary disks, as well as an unexpected flux signal of $\sim$4\% from the secondary star. The energy output from this companion indicates the presence of a compact circum-companion accretion disk, which is likely the origin of the fast outflow detected in H$\alpha$. Our image provides the most detailed view into the heart of a dusty circumstellar disk to date. Our results demonstrate that binary evolution processes and circumstellar disk evolution can be studied in detail in space and over time.Comment: PR @ http://www.eso.org/public/news/eso1608

An interferometric study of the post-AGB binary 89 Herculis. II Radiative transfer models of the circumbinary disk

The presence of disks and outflows is widespread among post-AGB binaries. In the first paper of this series, a surprisingly large fraction of optical light was found to be resolved in the 89 Her post-AGB system. The data showed this flux to arise from close to the central binary. Scattering off the inner rim of the circumbinary disk, or in a dusty outflow were suggested as two possible origins. With detailed dust radiative transfer models of the disk we aim to discriminate between these two configurations. By including Herschel/SPIRE photometry, we extend the SED such that it now fully covers UV to sub-mm wavelengths. The MCMax radiative transfer code is used to create a large grid of disk models. Our models include a self-consistent treatment of dust settling as well as of scattering. A Si-rich composition with two additional opacity sources, metallic Fe or amorphous C, are tested. The SED is fit together with mid-IR (MIDI) visibilities as well as the optical and near-IR visibilities of Paper I, to constrain the structure of the disk and in particular of its inner rim. The near-IR visibility data require a smooth inner rim, here obtained with a two-power-law parameterization of the radial surface density distribution. A model can be found that fits all the IR photometric and interferometric data well, with either of the two continuum opacity sources. Our best-fit passive models are characterized by a significant amount of mm-sized grains, which are settled to the midplane of the disk. Not a single disk model fits our data at optical wavelengths though, the reason being the opposing constraints imposed by the optical and near-IR interferometric data. A geometry in which a passive, dusty, and puffed-up circumbinary disk is present, can reproduce all the IR but not the optical observations of 89 Her. Another dusty, outflow or halo, component therefore needs to be added to the system.Comment: 15 pages, in pres