6m04

Structure of the human homo-hexameric LRRC8D channel at 4.36 Angstroms

spinqualitylabelsall models 6m04, resolution 4.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.36Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of the five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC). LRRC8A and at least one of the other LRRC8 isoforms assemble into heteromers to generate VRAC transport activities. Despite the availability of the LRRC8A structures, the structural basis of how LRRC8 isoforms other than LRRC8A contribute to the functional diversity of VRAC has remained elusive. Here, we present the structure of the human LRRC8D isoform, which enables the permeation of organic substrates through VRAC. The LRRC8D homo-hexamer structure displays a two-fold symmetric arrangement, and together with a structure-based electrophysiological analysis, revealed two key features. The pore constriction on the extracellular side is wider than that in the LRRC8A structures, which may explain the increased permeability of organic substrates. Furthermore, an N-terminal helix protrudes into the pore from the intracellular side and may be critical for gating. Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation.,Nakamura R, Numata T, Kasuya G, Yokoyama T, Nishizawa T, Kusakizako T, Kato T, Hagino T, Dohmae N, Inoue M, Watanabe K, Ichijo H, Kikkawa M, Shirouzu M, Jentsch TJ, Ishitani R, Okada Y, Nureki O Commun Biol. 2020 May 15;3(1):240. doi: 10.1038/s42003-020-0951-z. PMID:32415200 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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