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Nature - Issue - science feeds

Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all


Hillary Clinton will make a fine US president


And not only because she is not Donald Trump.

One sharp edge does not a tool make


Capuchin monkeys have been observed smashing stones to produce flakes ­ — but why they do so remains a mystery.

Women need to be seen and heard at conferences


A neuroscience initiative is boosting the number of female invited speakers at meetings. Other disciplines should do the same.

Neurotechnology: Paralysed man with implant feels touch


A brain implant that is wired to a robotic arm has allowed a paralysed man to feel touch on the arm's fingers.Robert Gaunt at the University of Pittsburgh in Pennsylvania and his colleagues placed electrodes in the brain of Nathan Copeland (pictured), whose legs

Astronomy: Two stars have three disks


Young stars are surrounded by a rotating disk of gas and dust, from which planets are born — but astronomers have discovered that one pair of young stars orbiting around each other has three disks, not just two.Christian Brinch at the University of Copenhagen

Drug discovery: Bacteria in humans yield drug


A small molecule produced by bacteria living naturally in people can help to combat a pathogen that is resistant to many antibiotics.Sean Brady at the Rockefeller University in New York City and his colleagues analysed the genomes of the human microbiota to identify genes

Climate change: Wildfires burn more US forest


Climate change resulting from human activities has nearly doubled the area burned by forest fires in the western United States over the past three decades.John Abatzoglou at the University of Idaho in Moscow and Park Williams at Columbia University in Palisades, New York, used

Chemistry: Meteorite makes good catalyst


An iron-based mineral from a meteorite can catalyse a chemical reaction that splits water into oxygen and hydrogen, which can be used as fuel.Some naturally occurring metallic minerals are known to have catalytic activity. Kevin Sivula and his colleagues at the Swiss Federal Institute

Animal cognition: Bees learn and 'teach' others


Bumblebees can learn to manipulate objects — and can pass their knowledge on to other bees.Lars Chittka at Queen Mary University of London and his colleagues presented bumblebees (Bombus terrestris) with a disc that had been filled with sugar water and placed

Neuroscience: Why mole rats don't feel the heat


A gene variant could explain why naked mole rats are impervious to certain types of pain that most mammals experience when exposed to heat.In the nervous system, a peptide called nerve growth factor (NGF) mediates hypersensitivity to pain caused by heat. Gary Lewin at

Plant biology: RNA spray fights fungus


Spraying leaves from barley plants with a liquid containing long RNA molecules helps them to fend off fungal infection.A mechanism called RNA interference (RNAi) uses double-stranded RNA molecules to shut down the expression of specific genes. Karl-Heinz Kogel of the Justus Liebig University in

Electronics: Shortest transistor made


Researchers have built a transistor with a 'gate' just one nanometre long — one-fifth of the smallest length thought to be possible in silicon transistors.The semiconductor industry is reaching the limits of its capacity to shrink silicon-based transistors. Graphene and other '2D' materials are

Mars excitement, campus riots and a freeze on refrigerants


The week in science: 14–20 October 2016

Arecibo Observatory hit with discrimination lawsuit


Two former workers say that they were treated unfairly on the basis of age and disability.

The scientists who support Donald Trump


Science policy fades into background for many who back Republican candidate in US presidential race.

How Republicans reshaped the House science committee


Chairman Lamar Smith has turned once-placid panel into investigative powerhouse.

Mouse eggs made from skin cells in a dish


Breakthrough raises call for debate over prospect of artificial human eggs.

Science group seeks to guide Silicon Valley philanthropists


Uncertain government funding drives effort to beef up private support for research.

Effort to wrangle geoscience data faces uncertain future


Five years in, the US EarthCube programme has struggled to deliver on its promises.

The polling crisis: How to tell what people really think


This year’s US presidential election is the toughest test yet for political polls as experts struggle to keep up with changing demographics and technology.

The power of prediction markets


Scientists are beginning to understand why these ‘mini Wall Streets’ work so well at forecasting election results — and how they sometimes fail.

There is a blind spot in AI research


Fears about the future impacts of artificial intelligence are distracting researchers from the real risks of deployed systems, argue Kate Crawford and Ryan Calo.

Natural history: Voices from the greenwood


Caspar Henderson applauds a paean to the brilliant forest ecologist Oliver Rackham.

Biomechanics: The wonders of whirl


John E. Moalli and Adam P. Summers relish a book on biomechanical spin, from wheels to free-falling felines.

Q&A: Lexi Jamieson Marsh and Ellen Currano: Face to face


Outside the hall containing the posters and exhibits at last month's Geological Society of America meeting in Denver, Colorado, was a surprise. A travelling photography exhibition displayed large, black-and-white portraits of women — wearing beards. To challenge perceptions of who is and is not a scientist, the Bearded Lady Project ( has photographed more than 75 female Earth scientists; a documentary will be released in early 2017. Filmmaker and project mastermind Lexi Jamieson Marsh and palaeobotanist Ellen Currano of the University of Wyoming in Laramie, who inspired the project, talk about 'invisible women', communities of inclusivity and rocking a moustache.

Deborah S. Jin 1968–2016


Pioneer of ultracold quantum physics.

Biodiversity: Two African elephant species, not just one


Your affirmation that the African forest elephant and the African savannah elephant are separate species (Nature537, 7; 10.1038/537007b2016) is timely. Earlier this month, the 17th Conference of Parties to the Convention on International Trade In Endangered Species (CITES) rejected

Social science: Include social equity in California Biohub


We have an idea for philanthropists Priscilla Chan and Mark Zuckerberg, who last month announced their first major investment in basic science: US$600 million for a Biohub in San Francisco, California.They aspire to 'advance human potential and promote equality' ( As members

China: Soil clean-up needs cash and clarity


China plans to curb soil pollution by 2020 and to bring environmental risks under control by 2030. In our view, several issues must be addressed for these goals to be realized. Meanwhile, a long-awaited law to prevent soil pollution should be enacted urgently.The ongoing

Species loss: learn from health metrics


The inability to quantify which threats matter most across species and ecosystems is a problem for policymaking and resource allocation (see S. L.Maxwellet al. Nature536, 143–145; 2016). Biodiversity conservation could learn from public-health metrics and go

Astrobiology: Martian dance of fiction and fact


In marking the H. G. Wells anniversary, you highlight what Carl Sagan dubbed the “dance” between science fiction and science fact (see's The War of the Worlds saw the Martian invasion stopped in its tracks by Earth pathogens (S. J.

For your information


Sounding out people who are already working in a field that interests you is a great way to gain valuable inside knowledge during your job search, says Peter Fiske.



The most important thing


You must remember this ...

Genomics: A matched set of frog sequences


A whole-genome duplication that occurred around 34 million years ago in the frog Xenopus laevis made generating a genome sequence for this valuable model organism a challenge. This obstacle has finally been overcome. See Article p.336

Astrophysics: Unexpected X-ray flares


Two sources of highly energetic flares have been discovered in archival X-ray data of 70 nearby galaxies. These flares have an undetermined origin and might represent previously unknown astrophysical phenomena. See Letter p.356

Cancer: A shocking protein complex


Heat-shock proteins have been found to form part of a large protein complex, called the epichaperome, that improves the survival of some cancer cells. This complex might offer a new target for cancer treatment. See Letter p.397

Drug discovery: Chemical diversity targets malaria


A molecule selected from a library of compounds that have structures similar to natural products targets several stages of the malarial parasite's life cycle, offering single-dose treatment of the disease in mouse models. See Article p.344

Optical physics: Speedy electrons exposed in a flash


A link has been established between high-frequency light emissions and electron oscillations induced in an insulator by a laser. This is a key step in efforts to make electronic devices that work faster than is currently possible. See Letter p.359

50 & 100 Years Ago


50 Years AgoThe question of how cells estimate their location within the body is closely related to that of why cells of a developing organism become differentiated ... We are now investigating the mechanism involved ... using abdominal segments of the pupa Galleria mellonella

Cell biology: The organelle replication connection


Live-cell imaging reveals that a functional interaction occurs between two different organelles: contact between the endoplasmic reticulum and mitochondria is needed for mitochondrial DNA replication and division.

Accurate de novo design of hyperstable constrained peptides


Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much

Genome evolution in the allotetraploid frog Xenopus laevis


To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into

Diversity-oriented synthesis yields novel multistage antimalarial inhibitors


Antimalarial drugs have thus far been chiefly derived from two sources—natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products

Frizzled proteins are colonic epithelial receptors for C. difficile toxin B


Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR–Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the

Ultraluminous X-ray bursts in two ultracompact companions to nearby elliptical galaxies


A flaring X-ray source was found near the galaxy NGC 4697 (ref. 1). Two brief flares were seen, separated by four years. During each flare, the flux increased by a factor of 90 on a timescale of about one minute. There is no associated optical source at the position of the flares, but if the source was at the distance of NGC 4697, then the luminosities of the flares were greater than 1039 erg per second. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar flares. We found two ultraluminous flaring sources in globular clusters or ultracompact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 × 1040 erg per second; the other flared five times to 1040 erg per second. The rise times of all of the flares were less than one minute, and the flares then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron-star or black-hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft γ repeaters that have repetitive flares of similar luminosities.

Multi-petahertz electronic metrology


The frequency of electric currents associated with charge carriers moving in the electronic bands of solids determines the speed limit of electronics and thereby that of information and signal processing. The use of light fields to drive electrons promises access to vastly higher frequencies than conventionally used, as electric currents can be induced and manipulated on timescales faster than that of the quantum dephasing of charge carriers in solids. This forms the basis of terahertz (1012 hertz) electronics in artificial superlattices, and has enabled light-based switches and sampling of currents extending in frequency up to a few hundred terahertz. Here we demonstrate the extension of electronic metrology to the multi-petahertz (1015 hertz) frequency range. We use single-cycle intense optical fields (about one volt per ångström) to drive electron motion in the bulk of silicon dioxide, and then probe its dynamics by using attosecond (10−18 seconds) streaking to map the time structure of emerging isolated attosecond extreme ultraviolet transients and their optical driver. The data establish a firm link between the emission of the extreme ultraviolet radiation and the light-induced intraband, phase-coherent electric currents that extend in frequency up to about eight petahertz, and enable access to the dynamic nonlinear conductivity of silicon dioxide. Direct probing, confinement and control of the waveform of intraband currents inside solids on attosecond timescales establish a method of realizing multi-petahertz coherent electronics. We expect this technique to enable new ways of exploring the interplay between electron dynamics and the structure of condensed matter on the atomic scale.

Real-space investigation of energy transfer in heterogeneous molecular dimers


Given its central role in photosynthesis and artificial energy-harvesting devices, energy transfer has been widely studied using optical spectroscopy to monitor excitation dynamics and probe the molecular-level control of energy transfer between coupled molecules. However, the spatial resolution of conventional optical spectroscopy is limited to a few hundred nanometres and thus cannot reveal the nanoscale spatial features associated with such processes. In contrast, scanning tunnelling luminescence spectroscopy has revealed the energy dynamics associated with phenomena ranging from single-molecule electroluminescence, absorption of localized plasmons and quantum interference effects to energy delocalization and intervalley electron scattering with submolecular spatial resolution in real space. Here we apply this technique to individual molecular dimers that comprise a magnesium phthalocyanine and a free-base phthalocyanine (MgPc and H2Pc) and find that locally exciting MgPc with the tunnelling current of the scanning tunnelling microscope generates a luminescence signal from a nearby H2Pc molecule as a result of resonance energy transfer from the former to the latter. A reciprocating resonance energy transfer is observed when exciting the second singlet state (S2) of H2Pc, which results in energy transfer to the first singlet state (S1) of MgPc and final funnelling to the S1 state of H2Pc. We also show that tautomerization of H2Pc changes the energy transfer characteristics within the dimer system, which essentially makes H2Pc a single-molecule energy transfer valve device that manifests itself by blinking resonance energy transfer behaviour.

Asthenosphere rheology inferred from observations of the 2012 Indian Ocean earthquake


The concept of a weak asthenospheric layer underlying Earth’s mobile tectonic plates is fundamental to our understanding of mantle convection and plate tectonics. However, little is known about the mechanical properties of the asthenosphere (the part of the upper mantle below the lithosphere) underlying the oceanic crust, which covers about 60 per cent of Earth’s surface. Great earthquakes cause large coseismic crustal deformation in areas hundreds of kilometres away from and below the rupture area. Subsequent relaxation of the earthquake-induced stresses in the viscoelastic upper mantle leads to prolonged postseismic crustal deformation that may last several decades and can be recorded with geodetic methods. The observed postseismic deformation helps us to understand the rheological properties of the upper mantle, but so far such measurements have been limited to continental-plate boundary zones. Here we consider the postseismic deformation of the very large (moment magnitude 8.6) 2012 Indian Ocean earthquake to provide by far the most direct constraint on the structure of oceanic mantle rheology. In the first three years after the Indian Ocean earthquake, 37 continuous Global Navigation Satellite Systems stations in the region underwent horizontal northeastward displacements of up to 17 centimetres in a direction similar to that of the coseismic offsets. However, a few stations close to the rupture area that had experienced subsidence of up to about 4 centimetres during the earthquake rose by nearly 7 centimetres after the earthquake. Our three-dimensional viscoelastic finite-element models of the post-earthquake deformation show that a thin (30–200 kilometres), low-viscosity (having a steady-state Maxwell viscosity of (0.5–10) × 1018 pascal seconds) asthenospheric layer beneath the elastic oceanic lithosphere is required to produce the observed postseismic uplift.

Upper-mantle water stratification inferred from observations of the 2012 Indian Ocean earthquake


Water, the most abundant volatile in Earth’s interior, preserves the young surface of our planet by catalysing mantle convection, lubricating plate tectonics and feeding arc volcanism. Since planetary accretion, water has been exchanged between the hydrosphere and the geosphere, but its depth distribution in the mantle remains elusive. Water drastically reduces the strength of olivine and this effect can be exploited to estimate the water content of olivine from the mechanical response of the asthenosphere to stress perturbations such as the ones following large earthquakes. Here, we exploit the sensitivity to water of the strength of olivine, the weakest and most abundant mineral in the upper mantle, and observations of the exceptionally large (moment magnitude 8.6) 2012 Indian Ocean earthquake to constrain the stratification of water content in the upper mantle. Taking into account a wide range of temperature conditions and the transient creep of olivine, we explain the transient deformation in the aftermath of the earthquake that was recorded by continuous geodetic stations along Sumatra as the result of water- and stress-activated creep of olivine. This implies a minimum water content of about 0.01 per cent by weight—or 1,600 H atoms per million Si atoms—in the asthenosphere (the part of the upper mantle below the lithosphere). The earthquake ruptured conjugate faults down to great depths, compatible with dry olivine in the oceanic lithosphere. We attribute the steep rheological contrast to dehydration across the lithosphere–asthenosphere boundary, presumably by buoyant melt migration to form the oceanic crust.

A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns


Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.

Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour


The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections. Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood. A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system, that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision. The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life. Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei, cortical lesions have suggested that the visual cortex might also be involved. Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment, is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function, to plastically adapt the execution of innate motor behaviours.

Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts


Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7.09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary.

Fetal liver endothelium regulates the seeding of tissue-resident macrophages


Macrophages are required for normal embryogenesis, tissue homeostasis and immunity against microorganisms and tumours. Adult tissue-resident macrophages largely originate from long-lived, self-renewing embryonic precursors and not from haematopoietic stem-cell activity in the bone marrow. Although fate-mapping studies have uncovered a great amount of detail on the origin and kinetics of fetal macrophage development in the yolk sac and liver, the molecules that govern the tissue-specific migration of these cells remain completely unknown. Here we show that an endothelium-specific molecule, plasmalemma vesicle-associated protein (PLVAP), regulates the seeding of fetal monocyte-derived macrophages to tissues in mice. We found that PLVAP-deficient mice have completely normal levels of both yolk-sac- and bone-marrow-derived macrophages, but that fetal liver monocyte-derived macrophage populations were practically missing from tissues. Adult PLVAP-deficient mice show major alterations in macrophage-dependent iron recycling and mammary branching morphogenesis. PLVAP forms diaphragms in the fenestrae of liver sinusoidal endothelium during embryogenesis, interacts with chemoattractants and adhesion molecules and regulates the egress of fetal liver monocytes to the systemic vasculature. Thus, PLVAP selectively controls the exit of macrophage precursors from the fetal liver and, to our knowledge, is the first molecule identified in any organ as regulating the migratory events during embryonic macrophage ontogeny.

The epichaperome is an integrated chaperome network that facilitates tumour survival


Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes—dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis. Such limitations have led to a bottleneck in our understanding of chaperome-related disease biology and in the development of chaperome-targeted cancer treatment. Here we examined the chaperome complexes in a large set of tumour specimens. The methods used maintained the endogenous native state of tumours and we exploited this to investigate the molecular characteristics and composition of the chaperome in cancer, the molecular factors that drive chaperome networks to crosstalk in tumours, the distinguishing factors of the chaperome in tumours sensitive to pharmacologic inhibition, and the characteristics of tumours that may benefit from chaperome therapy. We find that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically ‘rewired’ to form a network of stable, survival-facilitating, high-molecular-weight complexes. The chaperones heat shock protein 90 (HSP90) and heat shock cognate protein 70 (HSC70) are nucleating sites for these physically and functionally integrated complexes. The results indicate that these tightly integrated chaperome units, here termed the epichaperome, can function as a network to enhance cellular survival, irrespective of tissue of origin or genetic background. The epichaperome, present in over half of all cancers tested, has implications for diagnostics and also provides potential vulnerability as a target for drug intervention.

Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne


The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This ‘ubiquitin code’ determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system. Here we reveal how the deubiquitinase Cezanne (also known as OTUD7B) specifically targets Lys11-linked polyubiquitin. Crystal structures of Cezanne alone and in complex with monoubiquitin and Lys11-linked diubiquitin, in combination with hydrogen–deuterium exchange mass spectrometry, enable us to reconstruct the enzymatic cycle in great detail. An intricate mechanism of ubiquitin-assisted conformational changes activates the enzyme, and while all chain types interact with the enzymatic S1 site, only Lys11-linked chains can bind productively across the active site and stimulate catalytic turnover. Our work highlights the plasticity of deubiquitinases and indicates that new conformational states can occur when a true substrate, such as diubiquitin, is bound at the active site.

Atomic structure of the entire mammalian mitochondrial complex I


Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron–sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active–deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations.

X-ray structure of the human α4β2 nicotinic receptor


Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century. In addition to the receptors’ prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery. The overall architecture of the receptor was described in landmark studies of the nicotinic receptor isolated from the electric organ of Torpedo marmorata. Structures of a soluble ligand-binding domain have provided atomic-scale insights into receptor–ligand interactions, while high-resolution structures of other members of the pentameric receptor superfamily provide touchstones for an emerging allosteric gating mechanism. All available high-resolution structures are of homopentameric receptors. However, the vast majority of pentameric receptors (called Cys-loop receptors in eukaryotes) present physiologically are heteromeric. Here we present the X-ray crystallographic structure of the human α4β2 nicotinic receptor, the most abundant nicotinic subtype in the brain. This structure provides insights into the architectural principles governing ligand recognition, heteromer assembly, ion permeation and desensitization in this prototypical receptor class.

Addendum: Non-Joulian magnetostriction


Nature521, 340–343 (2015); doi: 10.1038/nature14459In this Letter, we showed that the volume of the Fe–Ga crystals we investigated is not conserved in the course of magnetostriction measurements; we termed this phenomenon non-Joulian magnetostriction (NJM), in contrast to