Volume 517 Number 7532


Time for the social sciences p.5

Governments that want the natural sciences to deliver more for society need to show greater commitment towards the social sciences and humanities.

doi: 10.1038/517005a


News Features

Science in 2015 p.12

From Gradzilla to coffee consumption: the research enterprise quantified for the year to come.

doi: 10.1038/517012a

News & Views

Entry signals control development p.24

Certain structural elements allow messenger RNAs not usually processed by the protein-synthesis apparatus to be translated. It now seems that they also control the expression of genes involved in embryonic development. See Article p.33

doi: 10.1038/nature14069

Like cartilage, but simpler p.25

The properties of articular cartilage, which lines bones in joints, depend partly on repulsion between components of the material. A new synthetic gel that mimics this feature has rare, direction-dependent properties. See Letter p.68

doi: 10.1038/517025a

Photosynthetic complex in close-up p.26

Photosystem II, a photosynthetic protein complex, is prone to X-ray damage during crystallography. A high-resolution structure of the undamaged complex now offers a detailed view of its catalytic centre. See Letter p.99

doi: 10.1038/nature14072

Diverted on the way to memory p.28

The finding that protein A of Staphylococcus aureus diverts the immune response so that it ineffectively responds to other structures from the bacterium explains the failure of ongoing attempts to develop working S. aureus vaccines.

doi: 10.1038/nature14083

It takes three to find the exit p.29

Mitotic cell division separates chromosome pairs into two genetically identical daughter cells. A study in fission yeast reveals that this separation is guided by the sequential activation of three phosphatase enzymes. See Letter p.94

doi: 10.1038/nature14080

Ocean circulation and rapid climate change p.30

High-resolution data on ocean circulation during the last glacial cycle suggest that the formation of North Atlantic Deep Water and associated heat transport may be more stable than previously thought. See Letter p.73

doi: 10.1038/nature14084


RNA regulons in Hox 5′ UTRs confer ribosome specificity to gene regulation p.33

Specialized ribosomes (with a particular protein composition) carry out translation of specific transcripts; analysis of Hox mRNA translation in mice reveals that unique RNA structural elements within their 5′ UTRs, including internal ribosome entry sites and translation inhibitory elements, are responsible for this specialized mode of translation.

doi: 10.1038/nature14010

Structure of a mammalian ryanodine receptor p.44

Using electron cryomicroscopy, the closed-state structure of rabbit RyR1 is determined at 4.8 Å resolution; analysis confirms that the RyR1 architecture consists of a six-transmembrane ion channel with a cytosolic α-solenoid scaffold, and suggests a mechanism for Ca2+-induced channel opening.

doi: 10.1038/nature13950

Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution p.50

Using electron cryomicroscopy, the structure of the closed-state rabbit ryanodine receptor RyR1 in complex with its modulator FKBP12 is solved at 3.8 Å; in addition to determining structural details of the ion-conducting channel domain, three previously uncharacterized domains help to reveal a molecular scaffold that allows long-range allosteric regulation of channel activities.

doi: 10.1038/nature14063


Higher-than-predicted saltation threshold wind speeds on Titan p.60

Wind tunnel experiments designed to simulate the conditions on Saturn’s moon Titan yield threshold wind speeds for particle saltation higher than those predicted by models derived from simulations of terrestrial-planet conditions; the results can be reconciled by modifying the models to take into account the low ratio of particle density to fluid density on Titan.

doi: 10.1038/nature14088

Observation of quantized conductance in neutral matter p.64

Quantized conductance in the transport of neutral atoms is observed in an optically produced channel — either a quantum point contact or a quantum wire — between two atom reservoirs; the lowest non-zero conductance value is the universal conductance quantum, the reciprocal of Planck’s constant.

doi: 10.1038/nature14049

An anisotropic hydrogel with electrostatic repulsion between cofacially aligned nanosheets p.68

Usually materials design focuses on attractive interactions, but here a hydrogel is described whose properties are dominated by electrostatic repulsion between negatively charged titanate nanosheets embedded within it; the material, inspired by articular cartilage, deforms easily when sheared parallel to the sheets but resists compressive forces applied orthogonally.

doi: 10.1038/nature14060

Hepatitis A virus and the origins of picornaviruses p.85

Hepatitis A virus is a picornavirus that causes significant morbidity but remains poorly understood; this paper now provides high-resolution crystal structures of both the mature and the empty hepatitis A virus particle, which show that the three-dimensional structure resembles insect picorna-like viruses.

doi: 10.1038/nature13806

Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation p.89

Intracellular ISG15 is an interferon (IFN)-α/β-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-α/β-dependent antiviral immunity in mice. We previously published a study describing humans with inherited ISG15 deficiency but without unusually severe viral diseases. We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-γ-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-α/β immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi–Goutières syndrome and spondyloenchondrodysplasia. We further show that an absence of intracellular ISG15 in the patients’ cells prevents the accumulation of USP18, a potent negative regulator of IFN-α/β signalling, resulting in the enhancement and amplification of IFN-α/β responses. Human ISG15, therefore, is not only redundant for antiviral immunity, but is a key negative regulator of IFN-α/β immunity. In humans, intracellular ISG15 is IFN-α/β-inducible not to serve as a substrate for ISGylation-dependent antiviral immunity, but to ensure USP18-dependent regulation of IFN-α/β and prevention of IFN-α/β-dependent autoinflammation.

doi: 10.1038/nature13801

A PP1–PP2A phosphatase relay controls mitotic progression p.94

The activation and coordination of phosphatase activity is important during mitotic exit; here, a mitotic phosphatase relay is described in fission yeast between the two major phosphatases, PP1 and PP2A, a mode of regulation that may be a feature of signalling networks across eukaryotes.

doi: 10.1038/nature14019

Native structure of photosystem II at 1.95 Å resolution viewed by femtosecond X-ray pulses p.99

Photosynthesis converts light energy into biologically useful chemical energy vital to life on Earth. The initial reaction of photosynthesis takes place in photosystem II (PSII), a 700-kilodalton homodimeric membrane protein complex that catalyses photo-oxidation of water into dioxygen through an S-state cycle of the oxygen evolving complex (OEC). The structure of PSII has been solved by X-ray diffraction (XRD) at 1.9 ångström resolution, which revealed that the OEC is a Mn4CaO5-cluster coordinated by a well defined protein environment. However, extended X-ray absorption fine structure (EXAFS) studies showed that the manganese cations in the OEC are easily reduced by X-ray irradiation, and slight differences were found in the Mn–Mn distances determined by XRD, EXAFS and theoretical studies. Here we report a ‘radiation-damage-free’ structure of PSII from Thermosynechococcus vulcanus in the S1 state at a resolution of 1.95 ångströms using femtosecond X-ray pulses of the SPring-8 ångström compact free-electron laser (SACLA) and hundreds of large, highly isomorphous PSII crystals. Compared with the structure from XRD, the OEC in the X-ray free electron laser structure has Mn–Mn distances that are shorter by 0.1–0.2 ångströms. The valences of each manganese atom were tentatively assigned as Mn1D(iii), Mn2C(iv), Mn3B(iv) and Mn4A(iii), based on the average Mn–ligand distances and analysis of the Jahn–Teller axis on Mn(iii). One of the oxo-bridged oxygens, O5, has significantly longer distances to Mn than do the other oxo-oxygen atoms, suggesting that O5 is a hydroxide ion instead of a normal oxygen dianion and therefore may serve as one of the substrate oxygen atoms. These findings provide a structural basis for the mechanism of oxygen evolution, and we expect that this structure will provide a blueprint for the design of artificial catalysts for water oxidation.

doi: 10.1038/nature13991

Structure of an integral membrane sterol reductase from Methylomicrobium alcaliphilum p.104

Sterols are essential biological molecules in the majority of life forms. Sterol reductases including Δ14-sterol reductase (C14SR, also known as TM7SF2), 7-dehydrocholesterol reductase (DHCR7) and 24-dehydrocholesterol reductase (DHCR24) reduce specific carbon–carbon double bonds of the sterol moiety using a reducing cofactor during sterol biosynthesis. Lamin B receptor (LBR), an integral inner nuclear membrane protein, also contains a functional C14SR domain. Here we report the crystal structure of a Δ14-sterol reductase (MaSR1) from the methanotrophic bacterium Methylomicrobium alcaliphilum 20Z (a homologue of human C14SR, LBR and DHCR7) with the cofactor NADPH. The enzyme contains ten transmembrane segments (TM1–10). Its catalytic domain comprises the carboxy-terminal half (containing TM6–10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. Comparison with a soluble steroid 5β-reductase structure suggests that the reducing end of NADPH meets the sterol substrate at the juncture of the two pockets. A sterol reductase activity assay proves that MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate, demonstrating functional conservation to human C14SR. Therefore, our structure as a prototype of integral membrane sterol reductases provides molecular insight into mutations in DHCR7 and LBR for inborn human diseases.

doi: 10.1038/nature13797