资源环境科技发展态势分析平台

The structure of human ACAT1 in complex with the inhibitor nevanimibe is resolved by cryo-electron microscopy.

Triacylglycerols store metabolic energy in organisms and have industrial uses as foods and fuels. Excessive accumulation of triacylglycerols in humans causes obesity and is associated with metabolic diseases(1). Triacylglycerol synthesis is catalysed by acyl-CoA diacylglycerol acyltransferase (DGAT) enzymes(2-4), the structures and catalytic mechanisms of which remain unknown. Here we determined the structure of dimeric human DGAT1, a member of the membrane-bound O-acyltransferase (MBOAT) family, by cryo-electron microscopy at approximately 3.0 angstrom resolution. DGAT1 forms a homodimer through N-terminal segments and a hydrophobic interface, with putative active sites within the membrane region. A structure obtained with oleoyl-CoA substrate resolved at approximately 3.2 angstrom shows that the CoA moiety binds DGAT1 on the cytosolic side and the acyl group lies deep within a hydrophobic channel, positioning the acyl-CoA thioester bond near an invariant catalytic histidine residue. The reaction centre is located inside a large cavity, which opens laterally to the membrane bilayer, providing lipid access to the active site. A lipid-like density-possibly representing an acyl-acceptor molecule-is located within the reaction centre, orthogonal to acyl-CoA. Insights provided by the DGAT1 structures, together with mutagenesis and functional studies, provide the basis for a model of the catalysis of triacylglycerol synthesis by DGAT.

Cryo-electron microscopy structures and functional and mutagenesis studies provide insights into the catalysis of triacylglycerol synthesis by human acyl-CoA diacylglycerol acyltransferase at its intramembrane active site.

Intracellular replication of the deadly pathogen Mycobacterium tuberculosis relies on the production of small organic molecules called siderophores that scavenge iron from host proteins(1). M. tuberculosis produces two classes of siderophore, lipid-bound mycobactin and water-soluble carboxymycobactin(2,3). Functional studies have revealed that iron-loaded carboxymycobactin is imported into the cytoplasm by the ATP binding cassette (ABC) transporter IrtAB(4), which features an additional cytoplasmic siderophore interaction domain(5). However, the predicted ABC exporter fold of IrtAB is seemingly contradictory to its import function. Here we show that membrane-reconstituted IrtAB is sufficient to import mycobactins, which are then reduced by the siderophore interaction domain to facilitate iron release. Structure determination by X-ray crystallography and cryo-electron microscopy not only confirms that IrtAB has an ABC exporter fold, but also reveals structural peculiarities at the transmembrane region of IrtAB that result in a partially collapsed inward-facing substrate-binding cavity. The siderophore interaction domain is positioned in close proximity to the inner membrane leaflet, enabling the reduction of membrane-inserted mycobactin. Enzymatic ATPase activity and in vivo growth assays show that IrtAB has a preference for mycobactin over carboxymycobactin as its substrate. Our study provides insights into an unusual ABC exporter that evolved as highly specialized siderophore-import machinery in mycobacteria.

Quantum cascade lasers are compact, electrically pumped light sources in the technologically important mid-infrared and terahertz region of the electromagnetic spectrum(1,2). Recently, the concept of topology(3) has been expanded from condensed matter physics into photonics(4), giving rise to a new type of lasing(5-8) using topologically protected photonic modes that can efficiently bypass corners and defects(4). Previous demonstrations of topological lasers have required an external laser source for optical pumping and have operated in the conventional optical frequency regime(5-8). Here we demonstrate an electrically pumped terahertz quantum cascade laser based on topologically protected valley edge states(9-11). Unlike topological lasers that rely on large-scale features to impart topological protection, our compact design makes use of the valley degree of freedom in photonic crystals(10,11), analogous to two-dimensional gapped valleytronic materials(12). Lasing with regularly spaced emission peaks occurs in a sharp-cornered triangular cavity, even if perturbations are introduced into the underlying structure, owing to the existence of topologically protected valley edge states that circulate around the cavity without experiencing localization. We probe the properties of the topological lasing modes by adding different outcouplers to the topological cavity. The laser based on valley edge states may open routes to the practical use of topological protection in electrically driven laser sources.

A quantum internet that connects remote quantum processors(1,2) should enable a number of revolutionary applications such as distributed quantum computing. Its realization will rely on entanglement of remote quantum memories over long distances. Despite enormous progress(3-12), at present the maximal physical separation achieved between two nodes is 1.3 kilometres(10), and challenges for longer distances remain. Here we demonstrate entanglement of two atomic ensembles in one laboratory via photon transmission through city-scale optical fibres. The atomic ensembles function as quantum memories that store quantum states. We use cavity enhancement to efficiently create atom-photon entanglement(13-15) and we use quantum frequency conversion(16) to shift the atomic wavelength to telecommunications wavelengths. We realize entanglement over 22 kilometres of field-deployed fibres via two-photon interference(17,18) and entanglement over 50 kilometres of coiled fibres via single-photon interference(19). Our experiment could be extended to nodes physically separated by similar distances, which would thus form a functional segment of the atomic quantum network, paving the way towards establishing atomic entanglement over many nodes and over much longer distances.