Volume 524 Issue 7565

Editorials

Rise of the citizen scientist p.265

From the oceans to the soil, technology is changing the part that amateurs can play in research. But this greater involvement raises concerns that must be addressed.

doi: 10.1038/524265a

Portfolio boost p.265

People who fund or manage many research projects could do it better with mindful analysis.

doi: 10.1038/524265b

News

News Features

The cannabis experiment p.280

As marijuana use becomes more acceptable, researchers are scrambling to answer key questions about the drug.

doi: 10.1038/524280a

News & Views

Tagged tags engage disposal p.294

Damaged organelles called mitochondria were once thought to be disposed of by a simple signalling cascade. Cell-based analyses now reveal that a network of complicated molecular interactions initiates disposal. See Article p.309

doi: 10.1038/nature15199

Bumps in the road to therapeutic antibodies p.295

A human antibody against dengue virus serotype 2 has been shown to protect mice against disease. Structures of the antibody bound to the virus illuminate how it binds different viral forms to prevent virus entry into cells.

doi: 10.1038/524295a

Light opens pathways for nickel catalysis p.297

The report of a light-activated catalyst that generates usually inaccessible nickel intermediates provides a general strategy that might allow elusive catalytic reactions to be realized. See Letter p.330

doi: 10.1038/nature15200

Hypoxia response becomes crystal clear p.298

The crystal structures of two proteins that respond to reduced tissue oxygen levels — hypoxia-inducible factors — provide insight into their function and reveal sites for rational drug design. See Article p.303

doi: 10.1038/nature14641

Multiple origins of mountain life p.300

A study of DNA sequences from more than 1,800 organisms on Mount Kinabalu in Borneo reveals the evolutionary mechanisms that led to the mountain's high and unique biodiversity. See Letter p.347

doi: 10.1038/nature14645

Mystery survivor of a supermassive black hole p.301

The G2 cloud in our Galaxy's core has survived an encounter with the central black hole and failed to trigger a major flare-up in the black hole's activity. A promising theory endeavours to explain the cloud's nature.

doi: 10.1038/524301a

Articles

Structural integration in hypoxia-inducible factors p.303

This study describes the long-awaited crystal structures for hypoxia-inducible factor (HIF) heterodimers, including complexes bound to small molecules and DNA; the HIF–ARNT architecture is distinct from the bHLH-PAS-containing CLOCK–BMAL1 heterodimer, and HIF mutations linked to cancer can be mapped to important structural regions, with the structures providing future reference for small-molecule drug discovery efforts.

doi: 10.1038/nature14883

The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy p.309

The PINK1 ubiquitin kinase is shown to recruit the two autophagy receptors NDP52 and OPTN to mitochondria to activate mitophagy directly, independently of the ubiquitin ligase parkin; once recruited to mitochondria, NDP52 and OPTN recruit autophagy initiation components, and parkin may amplify the phospho-ubiquitin signal generated by PINK1, resulting in robust autophagy induction.

doi: 10.1038/nature14893

Structural insights into µ-opioid receptor activation p.315

X-ray crystallography and molecular dynamics simulations of the μ-opioid receptor reveal the conformational changes in the extracellular and intracellular domains of this G-protein-coupled receptor that are associated with its activation.

doi: 10.1038/nature14886

Letters

Growing the gas-giant planets by the gradual accumulation of pebbles p.322

Gas-giant planets are widely thought to form from solid ‘cores’ of roughly ten Earth masses; simulations now show that such cores can be produced from ‘pebbles’ (centimetre-to-metre-sized objects) provided that the pebbles form sufficiently slowly, leading to the formation of one to four gas giants in agreement with the observed structure of the Solar System.

doi: 10.1038/nature14675

Switching on elusive organometallic mechanisms with photoredox catalysis p.330

Despite advances in carbon–carbon fragment couplings, the ability to forge carbon–oxygen bonds in a general fashion via nickel catalysis has been largely unsuccessful; here, visible-light-excited photoredox catalysts are shown to provide transient access to Ni(iii) species that readily participate in reductive elimination, leading to carbon–oxygen coupling.

doi: 10.1038/nature14875

Evolution of endemism on a young tropical mountain p.347

Investigating the evolutionary origins of montane biodiversity by sampling the entire biota from a single mountain, Mount Kinabalu in Borneo, allows for a better understanding not only of the origins of endemism, but also of this biota’s forecasted response to environmental change.

doi: 10.1038/nature14949

Mechanism of phospho-ubiquitin-induced PARKIN activation p.370

This study provides insights into conformational changes that lead to phospho-ubiquitin-induced PARKIN activation and how PARKIN is recruited to phospho-ubiquitin chains on mitochondria; the crystal structure of PARKIN in complex with phospho-ubiquitin also indicates that the pocket within PARKIN where phospho-ubiquitin binds carries amino acid residues that are mutated in patients with autosomal-recessive juvenile Parkinsonism.

doi: 10.1038/nature14879

Propagation of conformational changes during μ-opioid receptor activation p.375

µ-Opioid receptors (µORs) are G-protein-coupled receptors that are activated by a structurally diverse spectrum of natural and synthetic agonists including endogenous endorphin peptides, morphine and methadone. The recent structures of the μOR in inactive and agonist-induced active states (Huang et al., ref. 2) provide snapshots of the receptor at the beginning and end of a signalling event, but little is known about the dynamic sequence of events that span these two states. Here we use solution-state NMR to examine the process of μOR activation using a purified receptor (mouse sequence) preparation in an amphiphile membrane-like environment. We obtain spectra of the μOR in the absence of ligand, and in the presence of the high-affinity agonist BU72 alone, or with BU72 and a G protein mimetic nanobody. Our results show that conformational changes in transmembrane segments 5 and 6 (TM5 and TM6), which are required for the full engagement of a G protein, are almost completely dependent on the presence of both the agonist and the G protein mimetic nanobody, revealing a weak allosteric coupling between the agonist-binding pocket and the G-protein-coupling interface (TM5 and TM6), similar to that observed for the β2-adrenergic receptor. Unexpectedly, in the presence of agonist alone, we find larger spectral changes involving intracellular loop 1 and helix 8 compared to changes in TM5 and TM6. These results suggest that one or both of these domains may play a role in the initial interaction with the G protein, and that TM5 and TM6 are only engaged later in the process of complex formation. The initial interactions between the G protein and intracellular loop 1 and/or helix 8 may be involved in G-protein coupling specificity, as has been suggested for other family A G-protein-coupled receptors.

doi: 10.1038/nature14680