资源环境科技发展态势分析平台

Most magmatism occurring on Earth is conventionally attributed to passive mantle upwelling at mid-ocean ridges, to slab devolatilization at subduction zones, or to mantle plumes. However, the widespread Cenozoic intraplate volcanism in northeast China(1-3) and the young petit-spot volcanoes(4-7) offshore of the Japan Trench cannot readily be associated with any of these mechanisms. In addition, the mantle beneath these types of volcanism is characterized by zones of anomalously low seismic velocity above and below the transition zone(8-12) (a mantle level located at depths between 410 and 660 kilometres). A comprehensive interpretation of these phenomena is lacking. Here we show that most (or possibly all) of the intraplate and petit-spot volcanism and low-velocity zones around the Japanese subduction zone can be explained by the Cenozoic interaction of the subducting Pacific slab with a hydrous mantle transition zone. Numerical modelling indicates that 0.2 to 0.3 weight per cent of water dissolved in mantle minerals that are driven out from the transition zone in response to subduction and retreat of a tectonic plate is sufficient to reproduce the observations. This suggests that a critical amount of water may have accumulated in the transition zone around this subduction zone, as well as in others of the Tethyan tectonic belt(13) that are characterized by intraplate or petit-spot volcanism and low-velocity zones in the underlying mantle.

Elucidating the mechanism of sugar import requires a molecular understanding of how transporters couple sugar binding and gating events. Whereas mammalian glucose transporters (GLUTs) are specialists(1), the hexose transporter from the malaria parasite Plasmodium falciparum PfHT1(2,3) has acquired the ability to transport both glucose and fructose sugars as efficiently as the dedicated glucose (GLUT3) and fructose (GLUT5) transporters. Here, to establish the molecular basis of sugar promiscuity in malaria parasites, we determined the crystal structure of PfHT1 in complex with d-glucose at a resolution of 3.6 angstrom. We found that the sugar-binding site in PfHT1 is very similar to those of the distantly related GLUT3 and GLUT5 structures(4,5). Nevertheless, engineered PfHT1 mutations made to match GLUT sugar-binding sites did not shift sugar preferences. The extracellular substrate-gating helix TM7b in PfHT1 was positioned in a fully occluded conformation, providing a unique glimpse into how sugar binding and gating are coupled. We determined that polar contacts between TM7b and TM1 (located about 15 angstrom from d-glucose) are just as critical for transport as the residues that directly coordinate d-glucose, which demonstrates a strong allosteric coupling between sugar binding and gating. We conclude that PfHT1 has achieved substrate promiscuity not by modifying its sugar-binding site, but instead by evolving substrate-gating dynamics.

Crystal structure of the Plasmodium falciparum hexose transporter PfHT1 reveals the molecular basis of its ability to transport multiple types of sugar as efficiently as the dedicated mammalian glucose and fructose transporters.

Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, including diabetes and obesity(1). Structures of active receptors reveal peptide agonists engage deep within the receptor core, leading to an outward movement of extracellular loop 3 and the tops of transmembrane helices 6 and 7, an inward movement of transmembrane helix 1, reorganization of extracellular loop 2 and outward movement of the intracellular side of transmembrane helix 6, resulting in G-protein interaction and activation(2-6). Here we solved the structure of a non-peptide agonist, TT-OAD2, bound to the glucagon-like peptide-1 (GLP-1) receptor. Our structure identified an unpredicted non-peptide agonist-binding pocket in which reorganization of extracellular loop 3 and transmembrane helices 6 and 7 manifests independently of direct ligand interaction within the deep transmembrane domain pocket. TT-OAD2 exhibits biased agonism, and kinetics of G-protein activation and signalling that are distinct from peptide agonists. Within the structure, TT-OAD2 protrudes beyond the receptor core to interact with the lipid or detergent, providing an explanation for the distinct activation kinetics that may contribute to the clinical efficacy of this compound series. This work alters our understanding of the events that drive the activation of class B receptors.