6NZZ
LRRC8A-DCPIB in MSP1E3D1 nanodisc expanded state
Summary for 6NZZ
| Entry DOI | 10.2210/pdb6nzz/pdb |
| Related | 6NZW |
| EMDB information | 0562 0563 |
| Descriptor | Volume-regulated anion channel subunit LRRC8A, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, 4-{[(2S)-2-butyl-6,7-dichloro-2-cyclopentyl-1-oxo-2,3-dihydro-1H-inden-5-yl]oxy}butanoic acid (3 entities in total) |
| Functional Keywords | ion channel, volume-regulation, membrane protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 6 |
| Total formula weight | 585996.10 |
| Authors | Kern, D.M.,Hite, R.K.,Brohawn, S.G. (deposition date: 2019-02-14, release date: 2019-02-27, Last modification date: 2025-05-28) |
| Primary citation | Kern, D.M.,Oh, S.,Hite, R.K.,Brohawn, S.G. Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs. Elife, 8:-, 2019 Cited by PubMed Abstract: Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here, we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel. PubMed: 30775971DOI: 10.7554/eLife.42636 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.32 Å) |
Structure validation
Download full validation report
