8DXP
Structure of LRRC8C-LRRC8A(IL125) Chimera, Class 3
Summary for 8DXP
| Entry DOI | 10.2210/pdb8dxp/pdb |
| Related | 8DXN 8DXO |
| EMDB information | 27772 |
| Descriptor | Volume-regulated anion channel subunit LRRC8C,Volume-regulated anion channel subunit LRRC8A (1 entity in total) |
| Functional Keywords | lrrc8c, lrrc8a, swell, vrac, chimera, transport protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 7 |
| Total formula weight | 663233.86 |
| Authors | Takahashi, H.,Yamada, T.,Denton, J.S.,Strange, K.,Karakas, E. (deposition date: 2022-08-02, release date: 2023-03-22, Last modification date: 2024-10-30) |
| Primary citation | Takahashi, H.,Yamada, T.,Denton, J.S.,Strange, K.,Karakas, E. Cryo-EM structures of a LRRC8 chimera with native functional properties reveal heptameric assembly. Elife, 12:-, 2023 Cited by PubMed Abstract: Volume-regulated anion channels (VRACs) mediate volume regulatory Cl and organic solute efflux from vertebrate cells. VRACs are heteromeric assemblies of LRRC8A-E proteins with unknown stoichiometries. Homomeric LRRC8A and LRRC8D channels have a small pore, hexameric structure. However, these channels are either non-functional or exhibit abnormal regulation and pharmacology, limiting their utility for structure-function analyses. We circumvented these limitations by developing novel homomeric LRRC8 chimeric channels with functional properties consistent with those of native VRAC/LRRC8 channels. We demonstrate here that the LRRC8C-LRRC8A(IL1) chimera comprising LRRC8C and 25 amino acids unique to the first intracellular loop (IL1) of LRRC8A has a heptameric structure like that of homologous pannexin channels. Unlike homomeric LRRC8A and LRRC8D channels, heptameric LRRC8C-LRRC8A(IL1) channels have a large-diameter pore similar to that estimated for native VRACs, exhibit normal DCPIB pharmacology, and have higher permeability to large organic anions. Lipid-like densities are located between LRRC8C-LRRC8A(IL1) subunits and occlude the channel pore. Our findings provide new insights into VRAC/LRRC8 channel structure and suggest that lipids may play important roles in channel gating and regulation. PubMed: 36897307DOI: 10.7554/eLife.82431 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.7 Å) |
Structure validation
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