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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.


  
Ancient West African foragers in the context of African population history 期刊论文
NATURE, 2020, 577 (7792) : 665-+
作者:  Grunwald, Hannah A.;  Gantz, Valentino M.;  Poplawski, Gunnar;  Xu, Xiang-Ru S.;  Bier, Ethan;  Cooper, Kimberly L.
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Genome-wide ancestry profiles of four individuals, dating to 8,000 and 3,000 years before present, from the archaeological site of Shum Laka (Cameroon) shed light on the deep population history of sub-Saharan Africa.


Our knowledge of ancient human population structure in sub-Saharan Africa, particularly prior to the advent of food production, remains limited. Here we report genome-wide DNA data from four children-two of whom were buried approximately 8,000 years ago and two 3,000 years ago-from Shum Laka (Cameroon), one of the earliest known archaeological sites within the probable homeland of the Bantu language group(1-11). One individual carried the deeply divergent Y chromosome haplogroup A00, which today is found almost exclusively in the same region(12,13). However, the genome-wide ancestry profiles of all four individuals are most similar to those of present-day hunter-gatherers from western Central Africa, which implies that populations in western Cameroon today-as well as speakers of Bantu languages from across the continent-are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one that gave rise to at least four major lineages deep in the history of modern humans.


  
Addendum to the East Tennessee Technology Park Site-Wide Residual Contamination Remedial Investigation Work Plan Oak Ridge, Tennessee 科技报告
来源:US Department of Energy (DOE). 出版年: 2011
作者:  Pruess, K.
收藏  |  浏览/下载:2/0  |  提交时间:2019/04/05
RIWP Addendum  Site-Wide  Residual Contamination