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Structures of human pannexin 1 reveal ion pathways and mechanism of gating 期刊论文
NATURE, 2020
作者:  Krause, David W.;  Hoffmann, Simone;  Hu, Yaoming;  Wible, John R.;  Rougier, Guillermo W.;  Kirk, E. Christopher;  Groenke, Joseph R.;  Rogers, Raymond R.;  Rossie, James B.;  Schultz, Julia A.;  Evans, Alistair R.;  von Koenigswald, Wighart;  Rahantarisoa, Lydia J.
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

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.


  
Liquid flow and control without solid walls 期刊论文
NATURE, 2020, 581 (7806) : 58-+
作者:  Hellmuth, Susanne;  Stemmann, Olaf
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Wall-free liquid channels surrounded by an immiscible magnetic liquid can be used to create liquid circuitry or to transport human blood without damaging the blood cells by moving permanent magnets.


When miniaturizing fluidic circuitry, the solid walls of the fluid channels become increasingly important(1) because they limit the flow rates achievable for a given pressure drop, and they are prone to fouling(2). Approaches for reducing the wall interactions include hydrophobic coatings(3), liquid-infused porous surfaces(4-6), nanoparticle surfactant jamming(7), changes to surface electronic structure(8), electrowetting(9,10), surface tension pinning(11,12) and use of atomically flat channels(13). A better solution may be to avoid the solid walls altogether. Droplet microfluidics and sheath flow achieve this but require continuous flow of the central liquid and the surrounding liquid(1,14). Here we demonstrate an approach in which aqueous liquid channels are surrounded by an immiscible magnetic liquid, both of which are stabilized by a quadrupolar magnetic field. This creates self-healing, non-clogging, anti-fouling and near-frictionless liquid-in-liquid fluidic channels. Manipulation of the field provides flow control, such as valving, splitting, merging and pumping. The latter is achieved by moving permanent magnets that have no physical contact with the liquid channel. We show that this magnetostaltic pumping method can be used to transport whole human blood with very little damage due to shear forces. Haemolysis (rupture of blood cells) is reduced by an order of magnitude compared with traditional peristaltic pumping, in which blood is mechanically squeezed through a plastic tube. Our liquid-in-liquid approach provides new ways to transport delicate liquids, particularly when scaling channels down to the micrometre scale, with no need for high pressures, and could also be used for microfluidic circuitry.


  
Structural basis for selectivity and diversity in angiotensin II receptors 期刊论文
NATURE, 2017, 544 (7650) : 327-+
作者:  Zhang, Haitao;  Han, Gye Won;  Batyuk, Alexander;  Shchenko, Andrii I.;  White, Kate L.;  Patel, Nilkanth;  Sadybekov, Anastasiia;  Zamlynny, Beata;  Rudd, Michael T.;  Hollenstein, Kaspar;  Tolstikova, Alexandra;  White, Thomas A.;  Hunter, Mark S.;  Weierstall, Uwe;  Liu, Wei;  Babaoglu, Kerim;  Moore, Eric L.;  Katz, Ryan D.;  Shipman, Jennifer M.;  Garcia-Calvo, Margarita;  Sharma, Sujata;  Sheth, Payal;  Soisson, Stephen M.;  Stevens, Raymond C.;  Katritch, Vsevolod;  Herezov, Vadim C.
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/09