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The lipid dependence of the nicotinic acetylcholine receptor from the Torpedo electric organ has long been recognized, and one of the most consistent experimental observations is that, when reconstituted in membranes formed by zwitterionic phospholipids alone, exposure to agonist fails to elicit ion-flux activity. More recently, it has been suggested that the bacterial homolog ELIC (Erwinia chrysanthemi ligand-gated ion channel) has a similar lipid sensitivity. As a first step toward the elucidation of the structural basis of this phenomenon, we solved the structures of ELIC embedded in palmitoyl-oleoyl-phosphatidylcholine- (POPC-) only nanodiscs in both the unliganded (4.1-Å resolution) and agonist-bound (3.3 Å) states using single-particle cryoelectron microscopy. Comparison of the two structural models revealed that the largest differences occur at the level of loop C--at the agonist-binding sites--and the loops at the interface between the extracellular and transmembrane domains (ECD and TMD, respectively). On the other hand, the transmembrane pore is occluded in a remarkably similar manner in both structures. A straightforward interpretation of these findings is that POPC-only membranes frustrate the ECD-TMD coupling in such a way that the "conformational wave" of liganded-receptor gating takes place in the ECD and the interfacial M2-M3 linker but fails to penetrate the membrane and propagate into the TMD. Furthermore, analysis of the structural models and molecular simulations suggested that the higher affinity for agonists characteristic of the open- and desensitized-channel conformations results, at least in part, from the tighter confinement of the ligand to its binding site; this limits the ligand's fluctuations, and thus delays its escape into bulk solvent. [ABSTRACT FROM AUTHOR]

Ground-level ozone is adverse to human and vegetation health. High ground-level ozone concentrations usually occur over the United States in the summer, often referred to as the ozone season. However, observed monthly mean ozone concentrations in the southeastern United States were higher in October than July in 2010. The October ozone average in 2010 reached that of July in the past three decades (1980-2010). Our analysis shows that this extreme October ozone in 2010 over the Southeast is due in part to a dry and warm weather condition, which enhances photochemical production, air stagnation, and fire emissions. Observational evidence and modeling analysis also indicate that another significant contributor is enhanced emissions of biogenic isoprene, a major ozone precursor, from water-stressed plants under a dry and warm condition. The latter finding is corroborated by recent laboratory and field studies. This climate-induced biogenic control also explains the puzzling fact that the two extremes of high October ozone both occurred in the 2000s when anthropogenic emissions were lower than the 1980s and 1990s, in contrast to the observed decreasing trend of July ozone in the region. The occurrences of a drying and warming fall, projected by climate models, will likely lead to more active photochemistry, enhanced biogenic isoprene and fire emissions, an extension of the ozone season from summer to fall, and an increase of secondary organic aerosols in the Southeast, posing challenges to regional air quality management. [ABSTRACT FROM AUTHOR]