8DRQ
LRRC8A:C conformation 1 (round) LRR focus 3
Summary for 8DRQ
| Entry DOI | 10.2210/pdb8drq/pdb |
| Related | 8DR8 8DRA 8DRE 8DRK 8DRN 8DRO |
| EMDB information | 27674 27675 27676 27677 27678 27679 27681 |
| Descriptor | Volume-regulated anion channel subunit LRRC8A,Soluble cytochrome b562 (1 entity in total) |
| Functional Keywords | ion channel, volume-regulation, membrane protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 1 |
| Total formula weight | 105530.10 |
| Authors | Kern, D.M.,Brohawn, S.G. (deposition date: 2022-07-21, release date: 2023-03-08, Last modification date: 2024-06-12) |
| Primary citation | Kern, D.M.,Bleier, J.,Mukherjee, S.,Hill, J.M.,Kossiakoff, A.A.,Isacoff, E.Y.,Brohawn, S.G. Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels. Nat.Struct.Mol.Biol., 30:841-852, 2023 Cited by PubMed Abstract: Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume-regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are ubiquitously expressed in vertebrate cells as heteromeric assemblies of LRRC8A (SWELL1) and LRRC8B-E subunits. Channels of different subunit composition have distinct properties that explain the functional diversity of LRRC8 currents across cell types. However, the basis for heteromeric LRRC8 channel assembly and function is unknown. Here we leverage a fiducial-tagging strategy to determine single-particle cryo-EM structures of heterohexameric LRRC8A:C channels in multiple conformations. Compared to homomers, LRRC8A:C channels show pronounced differences in architecture due to heterotypic LRR interactions that displace subunits away from the conduction axis and poise the channel for activation. Structures and functional studies further reveal that lipids embedded in the channel pore block ion conduction in the closed state. These results provide insight into determinants for heteromeric LRRC8 channel assembly, activity and gating by lipids. PubMed: 36928458DOI: 10.1038/s41594-023-00944-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.16 Å) |
Structure validation
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