Volume 547 Number 7663

Editorials

News

News Features

News & Views

Stellar palaeontology p.284

A third gravitational-wave signal has been detected with confidence, produced again by the merger of two black holes. The combined data from these detections help to reveal the histories of the stars that left these black holes behind.

doi: 10.1038/547284a

Early signs of human presence in Australia p.285

It emerges that people reached Australia earlier than was thought. This finding casts light on the technology used by the travellers, and their possible interactions with animal species that became extinct. See Article p.306

doi: 10.1038/547285a

Chemistry and physics happily wed p.287

A major advance in the quantum theory of solids allows materials to be identified whose electronic states have a non-trivial topology. Such materials could have many computing and electronics applications. See Article p.298

doi: 10.1038/547287a

Nervous crosstalk to make antibodies p.288

Immune cells called T cells help immune-system B cells mature to produce antibodies. This entails signalling between cells using the molecule dopamine — a surprising immunological role for this neurotransmitter. See Article p.318

doi: 10.1038/nature23097

X-rays used to watch spins in 3D p.290

Complex nanoscale magnetization patterns have been resolved in 3D using advanced X-ray microscopy. This could spur the design of magnetic devices that have unique properties and functions. See Letter p.328

doi: 10.1038/547290a

Keeping it real to kill glioblastoma p.291

The results of in vitro and in vivo screens to identify genes that are essential for the survival of a type of brain cancer show almost no overlap, underlining the need for caution when interpreting in vitro studies. See Letter p355.

doi: 10.1038/nature23095

Analysis

Articles

Topological quantum chemistry p.298

A complete electronic band theory is presented that describes the global properties of all possible band structures and materials, and can be used to predict new topological insulators and semimetals.

doi: 10.1038/nature23268

TFH-derived dopamine accelerates productive synapses in germinal centres p.318

Human follicular helper T cells engaging in synaptic interactions with germinal centre B cells release dopamine stored in chromogranin B+ granules, causing rapid externalization of ICOS ligand, which in turn enhances CD40L delivery to the synaptic cleft and synaptic contact, and results in an accelerated response.

doi: 10.1038/nature23013

Letters

Transcription elongation factors represent in vivo cancer dependencies in glioblastoma p.355

An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer.

doi: 10.1038/nature23000

K2P2.1 (TREK-1)–activator complexes reveal a cryptic selectivity filter binding site p.364

Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK subfamily generate ‘leak’ currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit. In contrast to other potassium channels, K2P channels use a selectivity filter ‘C-type’ gate as the principal gating site. Despite recent advances, poor pharmacological profiles of K2P channels limit mechanistic and biological studies. Here we describe a class of small-molecule TREK activators that directly stimulate the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter. Structures of K2P2.1 (also known as TREK-1) alone and with two selective K2P2.1 (TREK-1) and K2P10.1 (TREK-2) activators—an N-aryl-sulfonamide, ML335, and a thiophene-carboxamide, ML402—define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation–π interaction that controls selectivity. Together, our data reveal a druggable K2P site that stabilizes the C-type gate ‘leak mode’ and provide direct evidence for K2P selectivity filter gating.

doi: 10.1038/nature22988