| | A combinatorial strategy for treating KRAS-mutant lung cancer
A systematic screen identifies FGFR1 signalling reactivation as an adaptive resistance mechanism after MEK inhibition specific for KRAS tumours, which can be targeted by combined inhibition with the clinically approved drugs trametinib and ponatinib. | A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase
This paper reports the identification of a new cereblon-modulating agent, CC-885, which targets the translation termination factor GSPT1 and demonstrates anti-tumour activity in patient-derived tumour cells; the crystal structure of the cereblon–DDB1–GSPT1–CC-885 complex reveals a common motif for cereblon-substrate recruitment. | Relativistic reverberation in the accretion flow of a tidal disruption event
Observations of reverberation arising from gravitationally redshifted iron Kα photons reflected off the inner accretion flow in a tidal disruption event demonstrate that X-rays originate from a region very close to the central black hole and not from a relativistic jet, as previously thought. | A Neptune-sized transiting planet closely orbiting a 5–10-million-year-old star
A fully formed, Neptune-sized planet is observed orbiting a young star, demonstrating that planets can form in less than 10 million years and may also experience inward migration on these timescales. | | Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution | A hot Jupiter orbiting a 2-million-year-old solar-mass T Tauri star
The radial velocities of a young star are measured, revealing the presence of a planet of mass about three-quarters that of Jupiter, orbiting its host star very closely, and thus demonstrating that ‘hot Jupiters’ can migrate inwards in less than two million years. | H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex
We have a limited understanding of how cells mark and identify newly replicated genomic loci that have a sister chromatid; here, unmethylated K20 in the tail of new histone H4 is shown to serve as a signature of post-replicative chromatin, which is specifically recognized by the homologous recombination complex TONSL–MMS22L. | Rates and mechanisms of bacterial mutagenesis from maximum-depth sequencing
Maximum-depth sequencing (MDS), a new method of detecting extremely rare variants within a bacterial population, is used to show that mutation rates in Escherichia coli vary across the genome by at least an order of magnitude, and also to uncover mechanisms of antibiotic-induced mutagenesis. | A CRISPR screen defines a signal peptide processing pathway required by flaviviruses
The endoplasmic-reticulum-associated signal peptidase complex is required for infection by numerous flaviviruses, including West Nile, Dengue and Zika viruses, but is not required for infection by other types of virus or for host protein synthesis. | Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens
A CRISPR screening approach shows that endoplasmic-reticulum (ER)-associated protein complexes, including the oligosaccharyltransferase (OST) protein complex, are important for infection by dengue virus and other related mosquito-borne flaviviruses, whereas hepatitis C virus is dependent on distinct entry factors, RNA binding proteins and FAD biosynthesis. | | | Brief Communications Arising | | | | | | Nature Outlook: Irritable Bowel Syndrome
Irritable bowel syndrome is one of the most common gastrointestinal disorders. As research slowly progresses, there is increased hope for treating, or perhaps preventing, this always unpleasant and in some cases severe condition.
Access the Outlook free online for six months.
Produced with support from Allergan plc | | | | | | | | | | | Searching for the rules that govern hadron construction
Advances in meson spectroscopy can enhance our understanding of how composite objects emerge from the fundamental underlying theory of interacting quarks and gluons, quantum chromodynamics.
Matthew R. Shepherd, Jozef J. Dudek, Ryan E. Mitchell | | Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain
Two spider toxins are shown to target the Nav1.1 subtype of sodium channel specifically, shedding light on the role of these channels in mechanical pain signalling.
Jeremiah D. Osteen, Volker Herzig, John Gilchrist et al. | Defining the consequences of genetic variation on a proteome-wide scale
The effect of natural genetic diversity on the proteome is characterized using an outbred mouse model with extensive variation; both transcripts and proteins from mouse livers are quantified to identify a large set of protein quantitative trait loci (pQTL), and mediation analysis identifies causal protein intermediates of distant pQTL.
Joel M. Chick, Steven C. Munger, Petr Simecek et al. | Crystal structure of the epithelial calcium channel TRPV6
The X-ray crystal structure of rat transient receptor potential channel TRPV6 at 3.25 Å resolution is reported, providing new insights into its assembly and calcium-selective permeation.
Kei Saotome, Appu K. Singh, Maria V. Yelshanskaya et al. | | AMPK–SKP2–CARM1 signalling cascade in transcriptional regulation of autophagy
An investigation into the nuclear events involved in autophagy regulation identifies the histone arginine methyltransferase CARM1 as a transcriptional co-activator of transcription factor TFEB; CARM1 levels are decreased by the SKP2-containing E3 ubiquitin ligase and increased during autophagy induction after nutrient starvation.
Hi-Jai R. Shin, Hyunkyung Kim, Sungryong Oh et al. | Solid-state harmonics beyond the atomic limit
A direct comparison of high harmonic generation in the solid and gas phases of Ar and Kr reveals higher harmonics in these rare-gas solids caused by strong interband couplings; evidence of recollisions implies that gas-phase techniques for attosecond pulse generation and orbital tomography could be adapted for solids.
Georges Ndabashimiye, Shambhu Ghimire, Mengxi Wu et al. | Proteome-wide covalent ligand discovery in native biological systems
Small molecules are powerful tools for investigating protein function, and can serve as leads for new therapeutics, but most human proteins lack known small-molecule ligands; here, a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins is reported.
Keriann M. Backus, Bruno E. Correia, Kenneth M. Lum et al. | Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex
The structure of the METTL3–METTL14 complex, which mediates N6-adenosine methylation of RNA, suggests that the METTL3 subunit is the catalytic core while METTL14 serves to bind RNA.
Xiang Wang, Jing Feng, Yuan Xue et al. | The first gravitational-wave source from the isolated evolution of two stars in the 40–100 solar mass range
Numerical simulations of the formation of binary black holes provide a framework within which to interpret the recent detection of the first gravitational-wave source and to predict the properties of subsequent binary-black-hole gravitational-wave events; the calculations predict detections of about 1,000 black-hole mergers per year once gravitational-wave observatories reach full sensitivity.
Krzysztof Belczynski, Daniel E. Holz, Tomasz Bulik et al. | Real-time dynamics of lattice gauge theories with a few-qubit quantum computer
A digital quantum simulation of a lattice gauge theory is performed on a quantum computer that consists of a few trapped-ion qubits; the model simulated is the Schwinger mechanism, which describes the creation of electron–positron pairs from vacuum.
Esteban A. Martinez, Christine A. Muschik, Philipp Schindler et al. | Negative capacitance in multidomain ferroelectric superlattices
Negative capacitance is observed in a model system of multidomain ferroelectric–dielectric superlattices; the multidomain state can increase the temperature range over which negative capacitance can be observed.
Pavlo Zubko, Jacek C. Wojdeł, Marios Hadjimichael et al. | Controlled fragmentation of multimaterial fibres and films via polymer cold-drawing
Cold-drawing of multimaterial fibres consisting of a brittle core embedded in a ductile polymer cladding results in controllable fragmentation of the core to produce uniformly sized rods parallel to the drawing direction for cylindrical geometries and narrow, parallel strips perpendicular to the drawing direction for flat geometries.
Soroush Shabahang, Guangming Tao, Joshua J. Kaufman et al. | Abiological catalysis by artificial haem proteins containing noble metals in place of iron
Replacing the iron atom in Fe-porphyrin IX proteins with a noble-metal atom enables the creation of enzymes that catalyse reactions not catalysed by native Fe-enzymes or other metalloenzymes; this approach could be used to generate other artificial enzymes that could catalyse a wide range of abiological transformations.
Hanna M. Key, Paweł Dydio, Douglas S. Clark et al. | A complement–microglial axis drives synapse loss during virus-induced memory impairment
People infected with West Nile virus often experience cognitive side effects including memory loss through unknown mechanisms; mice and humans infected with the virus experience a loss in hippocampal presynaptic terminals, which can be reversed by disrupting complement or microglia in mice.
Michael J. Vasek, Charise Garber, Denise Dorsey et al. | The bacteriophage ϕ29 tail possesses a pore-forming loop for cell membrane penetration
Structural and functional studies of the tail knob protein of bacteriophage ϕ29 shed light on how the phage breaches the membrane barrier and ejects its DNA genome into the host cell.
Jingwei Xu, Miao Gui, Dianhong Wang et al. | Hemi-fused structure mediates and controls fusion and fission in live cells
Super-resolution imaging provides direct evidence in live cells that membrane fusion and fission are mediated through an intermediate hemi-fused structure, where fusion and calcium/dynamin-dependent fission mechanisms compete to determine the transition of the intermediate to fusion or fission.
Wei-Dong Zhao, Edaeni Hamid, Wonchul Shin et al. | Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor
The cancer drug rocaglamide A cements the RNA helicase eIF4A on polypurine sequences and thereby prevents scanning of the 43S subunit along the messenger RNA, highlighting how a drug can act by stabilizing sequence-selective RNA–protein interactions.
Shintaro Iwasaki, Stephen N. Floor, Nicholas T. Ingolia | Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex
This study describes the structures of the IZUMO1 protein, found on sperm, and the JUNO protein, found on eggs, and sheds light on their roles in sperm–egg fusion during fertilization.
Halil Aydin, Azmiri Sultana, Sheng Li et al. | Structure of IZUMO1–JUNO reveals sperm–oocyte recognition during mammalian fertilization
The structure of the IZUMO1–JUNO complex, crucial for sperm–oocyte interaction during fertilization, is reported, providing a first step towards understanding the mechanics of the interaction.
Umeharu Ohto, Hanako Ishida, Elena Krayukhina et al. | | | | |
