7WSV
Cryo-EM structure of the N-terminal deletion mutant of human pannexin-1 in a nanodisc
Replaces: 7F8QSummary for 7WSV
| Entry DOI | 10.2210/pdb7wsv/pdb |
| EMDB information | 32768 |
| Descriptor | Pannexin-1 (1 entity in total) |
| Functional Keywords | atp release channel, vertebrate innexin homolog, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 7 |
| Total formula weight | 321688.07 |
| Authors | Kuzuya, M.,Hirano, H.,Hayashida, K.,Watanabe, M.,Kobayashi, K.,Tani, K.,Fujiyoshi, Y.,Oshima, A. (deposition date: 2022-02-01, release date: 2022-02-16, Last modification date: 2024-10-16) |
| Primary citation | 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 Cited by 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: 35133866DOI: 10.1126/scisignal.abg6941 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.5 Å) |
Structure validation
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