Current knowledge about the nucleocytoplasmic large DNA viruses (NCLDV) is largely derived from viral isolates co-cultivated with protists and algae. Building on the rapidly increasing wealth of publicly available metagenome data, we reconstructed 2,074 NCLDV genomes from sampling sites spanning the globe. This led to an 11-fold increase in phylogenetic diversity and a parallel 10-fold expansion in functional diversity. Analysing 58,023 metagenomic major capsid proteins of large and giant viruses revealed global distribution patterns and underlined their cosmopolitan nature. The discovered viral genomes encoded a wide range of proteins with putative roles in photosynthesis and diverse substrate transport processes, revealing host reprogramming as a likely common strategy in the NCLDV. Furthermore, horizontal gene transfer inferences connected viral lineages to diverse eukaryotic hosts. We anticipate that the vast diversity of NCLDV revealed here on a global scale will establish giant viruses as key ecosystem players across Earth's biomes, associated with most major eukaryotic lineages.

Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization, and affecting various downstream signalling pathways1,2. Although there is a wealth of structural information delineating the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-EM structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human β-arrestin 1 (βarr1ΔCT). We found that phosphorylation of NTSR1 was critical for obtaining a stable complex with βarr1ΔCT, and identified phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observed a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared to a structure of rhodopsin-arrestin-1, our structure displays an approximately 85° rotation of arrestin relative to the receptor. These findings highlight both conserved aspects but also the plasticity of arrestin–receptor interactions.

Following agonist activation, G-protein-coupled receptors (GPCRs) recruit β-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis1. Additionally, β-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins2. Here we present a cryo-electron microscopy (cryo-EM) structure of β-arrestin 1 (βarr1) in complex with muscarinic acetylcholine-2-receptor (M2R) reconstituted in lipid nanodiscs. The M2R–βarr1 structure shows a multimodal network of flexible interactions, including binding of the βarr1 N domain to phosphorylated receptor residues and βarr1 finger loop insertion into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric Go protein structure3. Moreover, the cryoEM map reveals that the βarr1 C-domain edge engages the lipid bilayer. Through atomistic simulations, biophysical, biochemical, and cellular assays, we show that the C-edge is critical for stable complex formation, βarr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest the cooperative interactions of β-arrestin with both the receptor and phospholipid bilayer contribute to its functional versatility.

Glycans have diverse physiological functions, ranging from energy storage and structural integrity to cell signalling and the regulation of intracellular processes1. Although biomass-derived carbohydrates (such as (D)-glucose, (D)-xylose and (D)-galactose) are extracted on commercial scales, and serve as renewable chemical feedstocks and building blocks2,3, there are many hundreds of distinct monosaccharides that typically cannot be isolated from their natural sources and must instead be prepared through multistep chemical or enzymatic syntheses4,5. These ‘rare’ sugars feature prominently in bioactive natural products and pharmaceuticals, including many FDA-approved antiviral, antibacterial, anti-cancer and cardiac drugs6,7. Here we report the preparation of rare sugar isomers directly from biomass carbohydrates through site-selective epimerization reactions. Mechanistic studies establish that these reactions proceed under kinetic control, through sequential steps of hydrogen atom abstraction and hydrogen atom donation mediated by two distinct catalysts. This synthetic strategy provides concise and potentially extensive access to this valuable class of natural compounds.

For the past 150 years, the prevailing view of the local interstellar medium was based on a peculiarity known as Gould’s Belt1–4, an expanding ring of young stars, gas and dust, tilted about 20 degrees to the Galactic plane. Still, the physical relation between local gas clouds has remained practically unknown because the distance accuracy to clouds is of the same order as, or larger than, their sizes5–7. With the advent of large photometric surveys8 and astrometric survey9 this situation has changed10. Here we report the three-dimensional structure of all local cloud complexes. We find a narrow and coherent 2.7-kiloparsec arrangement of dense gas in the solar neighbourhood that contains many of the clouds thought to be associated with the Gould Belt. This finding is inconsistent with the notion that these clouds are part of a ring, disputing the Gould Belt model. The new structure comprises the majority of nearby star-forming regions, has an aspect ratio of about 1:20, and contains about three million solar masses of gas. Remarkably, the new structure appears to be undulating and its three-dimensional structure is well described by a damped sinusoidal wave on the plane of the Milky Way, with an average period of about 2 kiloparsecs and a maximum amplitude of about 160 parsecs.