CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

Na+-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na+-coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode

Measurements of W-value, Mobility and Gas Gain in Electronegative Gaseous CS2 and CS2 Gas Mixtures

W-value, mobility and gas gain measurements have been carried out in electronegative gaseous CS2 and CS2 gas mixtures at a pressure of 40 Torr making use of a single electron proportional counter method. The experimental results have revealed that W-values obtained for CS2 (40 Torr), CS2-CF4 (30 Torr - 10 Torr), CS2-Ar (35 Torr - 5 Torr), CS2-Ne (35 Torr - 5 Torr) and CS2-He (35 Torr - 5 Torr) gas mixtures are 21.1+/-2.7(stat)+/-3(syst) eV, 16.4+/-1.8(stat)+/-2(syst) eV, 13.1+/-1.5(stat)+/-2(syst) eV, 16.3+/-3.0(stat)+/-3(syst) eV and 17.3+/-3.0(stat)+/-3(syst) eV. The mobility for all CS2 gas mixtures was found to be slightly greater and the gas gain was found to be significantly greater relative to pure CS2

Low-mass dark matter search results from full exposure of PandaX-I experiment

We report the results of a weakly-interacting massive particle (WIMP) dark matter search using the full 80.1\;live-day exposure of the first stage of the PandaX experiment (PandaX-I) located in the China Jin-Ping Underground Laboratory. The PandaX-I detector has been optimized for detecting low-mass WIMPs, achieving a photon detection efficiency of 9.6\%. With a fiducial liquid xenon target mass of 54.0\,kg, no significant excess event were found above the expected background. A profile likelihood analysis confirms our earlier finding that the PandaX-I data disfavor all positive low-mass WIMP signals reported in the literature under standard assumptions. A stringent bound on the low mass WIMP is set at WIMP mass below 10\,GeV/c$^2$, demonstrating that liquid xenon detectors can be competitive for low-mass WIMP searches.Comment: v3 as accepted by PRD. Minor update in the text in response to referee comments. Separating Fig. 11(a) and (b) into Fig. 11 and Fig. 12. Legend tweak in Fig. 9(b) and 9(c) as suggested by referee, as well as a missing legend for CRESST-II legend in Fig. 12 (now Fig. 13). Same version as submitted to PR

Single particle electron microscopy analysis of the bovine anion exchanger 1 reveals a flexible linker connecting the cytoplasmic and membrane domains.

Anion exchanger 1 (AE1) is the major erythrocyte membrane protein that mediates chloride/bicarbonate exchange across the erythrocyte membrane facilitating CO₂ transport by the blood, and anchors the plasma membrane to the spectrin-based cytoskeleton. This multi-protein cytoskeletal complex plays an important role in erythrocyte elasticity and membrane stability. An in-frame AE1 deletion of nine amino acids in the cytoplasmic domain in a proximity to the membrane domain results in a marked increase in membrane rigidity and ovalocytic red cells in the disease Southeast Asian Ovalocytosis (SAO). We hypothesized that AE1 has a flexible region connecting the cytoplasmic and membrane domains, which is partially deleted in SAO, thus causing the loss of erythrocyte elasticity. To explore this hypothesis, we developed a new non-denaturing method of AE1 purification from bovine erythrocyte membranes. A three-dimensional (3D) structure of bovine AE1 at 2.4 nm resolution was obtained by negative staining electron microscopy, orthogonal tilt reconstruction and single particle analysis. The cytoplasmic and membrane domains are connected by two parallel linkers. Image classification demonstrated substantial flexibility in the linker region. We propose a mechanism whereby flexibility of the linker region plays a critical role in regulating red cell elasticity