The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

In vitro delivery of the diphtheria toxin catalytic (C) domain from the lumen of purified early endosomes to the external milieu requires the addition of both ATP and a cytosolic translocation factor (CTF) complex. Using the translocation of C-domain ADP-ribosyltransferase activity across the endosomal membrane as an assay, the CTF complex activity was 650–800-fold purified from human T cell and yeast extracts, respectively. The chaperonin heat shock protein (Hsp) 90 and thioredoxin reductase were identified by mass spectrometry sequencing in CTF complexes purified from both human T cell and yeast. Further analysis of the role played by these two proteins with specific inhibitors, both in the in vitro translocation assay and in intact cell toxicity assays, has demonstrated their essential role in the productive delivery of the C-domain from the lumen of early endosomes to the external milieu. These results confirm and extend earlier observations of diphtheria toxin C-domain unfolding and refolding that must occur before and after vesicle membrane translocation. In addition, results presented here demonstrate that thioredoxin reductase activity plays an essential role in the cytosolic release of the C-domain. Because analogous CTF complexes have been partially purified from mammalian and yeast cell extracts, results presented here suggest a common and fundamental mechanism for C-domain translocation across early endosomal membranes

TESS delivers its first Earth-sized planet and a warm sub-Neptune

The future of exoplanet science is bright, as TESS once again demonstrates with the discovery of its longest-period confirmed planet to date. We hereby present HD 21749b (TOI 186.01), a sub-Neptune in a 36-day orbit around a bright (V = 8.1) nearby (16 pc) K4.5 dwarf. TESS measures HD21749b to be 2.61$^{+0.17}_{-0.16}$ $R_{\oplus}$, and combined archival and follow-up precision radial velocity data put the mass of the planet at $22.7^{+2.2}_{-1.9}$ $M_{\oplus}$. HD 21749b contributes to the TESS Level 1 Science Requirement of providing 50 transiting planets smaller than 4 $R_{\oplus}$ with measured masses. Furthermore, we report the discovery of HD 21749c (TOI 186.02), the first Earth-sized ($R_p = 0.892^{+0.064}_{-0.058} R_{\oplus}$) planet from TESS. The HD21749 system is a prime target for comparative studies of planetary composition and architecture in multi-planet systems.Comment: Published in ApJ Letters; 5 figures, 1 tabl

The Magellan-TESS Survey I: Survey Description and Mid-Survey Results

One of the most significant revelations from Kepler is that roughly one-third of Sun-like stars host planets which orbit their stars within 100 days and are between the size of Earth and Neptune. How do these super-Earth and sub-Neptune planets form, what are they made of, and do they represent a continuous population or naturally divide into separate groups? Measuring their masses and thus bulk densities can help address these questions of their origin and composition. To that end, we began the Magellan-TESS Survey (MTS), which uses Magellan II/PFS to obtain radial velocity (RV) masses of 30 transiting exoplanets discovered by TESS and develops an analysis framework that connects observed planet distributions to underlying populations. In the past, RV measurements of small planets have been challenging to obtain due to the faintness and low RV semi-amplitudes of most Kepler systems, and challenging to interpret due to the potential biases in the existing ensemble of small planet masses from non-algorithmic decisions for target selection and observation plans. The MTS attempts to minimize these biases by focusing on bright TESS targets and employing a quantitative selection function and multi-year observing strategy. In this paper, we (1) describe the motivation and survey strategy behind the MTS, (2) present our first catalog of planet mass and density constraints for 25 TESS Objects of Interest (TOIs; 20 in our population analysis sample, five that are members of the same systems), and (3) employ a hierarchical Bayesian model to produce preliminary constraints on the mass-radius (M-R) relation. We find qualitative agreement with prior mass-radius relations but some quantitative differences (abridged). The the results of this work can inform more detailed studies of individual systems and offer a framework that can be applied to future RV surveys with the goal of population inferences.Comment: 101 pages (39 of main text and references, the rest an appendix of figures and tables). Submitted to AAS Journal

A planet within the debris disk around the pre-main-sequence star AU Microscopii

AU Microscopii (AU Mic) is the second closest pre main sequence star, at a distance of 9.79 parsecs and with an age of 22 million years. AU Mic possesses a relatively rare and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star, and with clumps exhibiting non-Keplerian motion. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic activity on the star. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3 sigma confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.Comment: Nature, published June 24th [author spelling name fix

The Multiplanet System TOI-421: A Warm Neptune and a Super Puffy Mini-Neptune Transiting a G9 V Star in a Visual Binary

We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations—comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echellé Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution Échelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements—and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P_b = 5.19672 ± 0.00049 days, a mass of M_b = 7.17 ± 0.66 M⊕, and a radius of R_b = 2.68^(+0.19)_(-0.18) R⊕, whereas the outer warm Neptune, TOI-421 c, has a period of Pc = 16.06819 ± 0.00035 days, a mass of M_c = 16.42^(+1.06)_(-1.04) M⊕, a radius of R_c = 5.09^(+0.16)_(-0.15) R⊕ and a density of ρ_c = 0.685^(+0.080)_(-0.072) g cm⁻³. With its characteristics, the outer planet (ρ_c = 0.685^(+0.080)_(-0.072) g cm⁻³) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Lyα transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed

The src Homology 3-Like Domain of the Diphtheria Toxin Repressor (DtxR) Modulates Repressor Activation through Interaction with the Ancillary Metal Ion-Binding Site

The diphtheria toxin repressor (DtxR) is a transition metal ion-activated repressor that acts as a global regulatory element in the control of iron-sensitive genes in Corynebacterium diphtheriae. We recently described (L. Sun, J. C. vanderSpek, and J. R. Murphy, Proc. Natl. Acad. Sci. USA 95:14985-14990, 1998) the isolation and in vivo characterization of a hyperactive mutant of DtxR, DtxR(E175K), that appeared to be constitutively active. We demonstrate here that while DtxR(E175K) remains active in vivo in the presence of 300 μM 2,2′dipyridyl, the purified repressor is, in fact, dependent upon low levels of transition metal ion to transit from the inactive apo form to the active metal ion-bound form of the repressor. Binding studies using 8-anilino-1-naphthalenesulfonic acid suggest that the E175K mutation stabilizes an intermediate of the molten-globule form of the repressor, increasing exposure of hydrophobic residues to solvent. We demonstrate that the hyperactive DtxR(E175K) phenotype is dependent upon an intact ancillary metal ion-binding site (site 1) of the repressor. These observations support the hypothesis that metal ion binding in the ancillary site facilitates the conversion of the inactive apo-repressor to its active, operator-binding conformation. Furthermore, these results support the hypothesis that the C-terminal src homology 3-like domain of DtxR plays an active role in the modulation of repressor activity

TOI-824 b: A New Planet on the Lower Edge of the Hot Neptune Desert

We report the detection of a transiting hot Neptune exoplanet orbiting TOI-824 (SCR J1448-5735), a nearby (d = 64 pc) K4V star, using data from the Transiting Exoplanet Survey Satellite. The newly discovered planet has a radius R p = 2.93 ± 0.20 R⊕ and an orbital period of 1.393 days. Radial velocity measurements using the Planet Finder Spectrograph and the High Accuracy Radial velocity Planet Searcher spectrograph confirm the existence of the planet, and we estimate its mass to be 18.47 ± 1.84 M⊕. The planet's mean density is ρp = 4.03-0.78+0.98 g cm-3, making it more than twice as dense as Neptune. TOI-824 b's high equilibrium temperature makes the planet likely to have a cloud-free atmosphere, and thus it is an excellent candidate for follow-up atmospheric studies. The detectability of TOI-824 b's atmosphere from both ground and space is promising and could lead to the detailed characterization of the most irradiated small planet at the edge of the hot Neptune desert that has retained its atmosphere to date