7DWB

Human Pannexin1 model

7DWB の概要

• エントリーDOI: 10.2210/pdb7dwb/pdb
• EMDBエントリー: 30880
• 分子名称: Pannexin-1 (1 entity in total)
• 機能のキーワード: plasma membrane, ion channel, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 343103.77

構造登録者

Zhang, S.S.,Yang, M.J. (登録日: 2021-01-17, 公開日: 2021-05-26, 最終更新日: 2024-10-23)

主引用文献

Zhang, S.,Yuan, B.,Lam, J.H.,Zhou, J.,Zhou, X.,Ramos-Mandujano, G.,Tian, X.,Liu, Y.,Han, R.,Li, Y.,Gao, X.,Li, M.,Yang, M.
Structure of the full-length human Pannexin1 channel and insights into its role in pyroptosis.
Cell Discov, 7:30-30, 2021

PubMed Abstract: Pannexin1 (PANX1) is a large-pore ATP efflux channel with a broad distribution, which allows the exchange of molecules and ions smaller than 1 kDa between the cytoplasm and extracellular space. In this study, we show that in human macrophages PANX1 expression is upregulated by diverse stimuli that promote pyroptosis, which is reminiscent of the previously reported lipopolysaccharide-induced upregulation of PANX1 during inflammasome activation. To further elucidate the function of PANX1, we propose the full-length human Pannexin1 (hPANX1) model through cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulation studies, establishing hPANX1 as a homo-heptamer and revealing that both the N-termini and C-termini protrude deeply into the channel pore funnel. MD simulations also elucidate key energetic features governing the channel that lay a foundation to understand the channel gating mechanism. Structural analyses, functional characterizations, and computational studies support the current hPANX1-MD model, suggesting the potential role of hPANX1 in pyroptosis during immune responses.

PubMed: 33947837
DOI: 10.1038/s41421-021-00259-0

実験手法

ELECTRON MICROSCOPY (3.15 Å)