Global S&T Development Trend Analysis Platform of Resources and Environment
Cryo-electron microscopy structures of the ATP-permeable channel pannexin 1 reveal a gating mechanism involving multiple distinct ion-conducting pathways.
Pannexin 1 (PANX1) is an ATP-permeable channel with critical roles in a variety of physiological functions such as blood pressure regulation(1), apoptotic cell clearance(2) and human oocyte development(3). Here we present several structures of human PANX1 in a heptameric assembly at resolutions of up to 2.8 angstrom, including an apo state, a caspase-7-cleaved state and a carbenoxolone-bound state. We reveal a gating mechanism that involves two ion-conducting pathways. Under normal cellular conditions, the intracellular entry of the wide main pore is physically plugged by the C-terminal tail. Small anions are conducted through narrow tunnels in the intracellular domain. These tunnels connect to the main pore and are gated by a long linker between the N-terminal helix and the first transmembrane helix. During apoptosis, the C-terminal tail is cleaved by caspase, allowing the release of ATP through the main pore. We identified a carbenoxolone-binding site embraced by W74 in the extracellular entrance and a role for carbenoxolone as a channel blocker. We identified a gap-junction-like structure using a glycosylation-deficient mutant, N255A. Our studies provide a solid foundation for understanding the molecular mechanisms underlying the channel gating and inhibition of PANX1 and related large-pore channels.
As anthropogenic climate change continues the risks to biodiversity will increase over time, with future projections indicating that a potentially catastrophic loss of global biodiversity is on the horizon(1-3). However, our understanding of when and how abruptly this climate-driven disruption of biodiversity will occur is limited because biodiversity forecasts typically focus on individual snapshots of the future. Here we use annual projections (from 1850 to 2100) of temperature and precipitation across the ranges of more than 30,000 marine and terrestrial species to estimate the timing of their exposure to potentially dangerous climate conditions. We project that future disruption of ecological assemblages as a result of climate change will be abrupt, because within any given ecological assemblage the exposure of most species to climate conditions beyond their realized niche limits occurs almost simultaneously. Under a high-emissions scenario (representative concentration pathway (RCP) 8.5), such abrupt exposure events begin before 2030 in tropical oceans and spread to tropical forests and higher latitudes by 2050. If global warming is kept below 2 degrees C, less than 2% of assemblages globally are projected to undergo abrupt exposure events of more than 20% of their constituent species
Using annual projections of temperature and precipitation to estimate when species will be exposed to potentially harmful climate conditions reveals that disruption of ecological assemblages as a result of climate change will be abrupt and could start as early as the current decade.