7F8J

Cryo-EM structure of human pannexin-1 in a nanodisc

7F8J の概要

• エントリーDOI: 10.2210/pdb7f8j/pdb
• EMDBエントリー: 31489
• 分子名称: Pannexin-1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (2 entities in total)
• 機能のキーワード: atp release channel, vertebrate innexin homolog, transport 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: 368580.23

構造登録者

Kuzuya, M.,Hirano, H.,Hayashida, K.,Watanabe, M.,Kobayashi, K.,Tani, K.,Fujiyoshi, Y.,Oshima, A. (登録日: 2021-07-02, 公開日: 2022-01-26, 最終更新日: 2025-06-25)

主引用文献

Kuzuya, M.,Hirano, H.,Hayashida, K.,Watanabe, M.,Kobayashi, K.,Terada, T.,Mahmood, M.I.,Tama, F.,Tani, K.,Fujiyoshi, Y.,Oshima, A.
Structures of human pannexin-1 in nanodiscs reveal gating mediated by dynamic movement of the N terminus and phospholipids.
Sci.Signal., 15:eabg6941-eabg6941, 2022

PubMed Abstract: Pannexin (PANX) family proteins form large-pore channels that mediate purinergic signaling. We analyzed the cryo-EM structures of human PANX1 in lipid nanodiscs to elucidate the gating mechanism and its regulation by the amino terminus in phospholipids. The wild-type channel has an amino-terminal funnel in the pore, but in the presence of the inhibitor probenecid, a cytoplasmically oriented amino terminus and phospholipids obstruct the pore. Functional analysis using whole-cell patch-clamp and oocyte voltage clamp showed that PANX1 lacking the amino terminus did not open and had a dominant negative effect on channel activity, thus confirming that the amino-terminal domain played an essential role in channel opening. These observations suggest that dynamic conformational changes in the amino terminus of human PANX1 are associated with lipid movement in and out of the pore. Moreover, the data provide insight into the gating mechanism of PANX1 and, more broadly, other large-pore channels.

PubMed: 35133866
DOI: 10.1126/scisignal.abg6941

実験手法

ELECTRON MICROSCOPY (3.6 Å)