8ga3 | pdb_00008ga3

CLC-ec1 R230C/L249C/C85A at pH 4.5 100mM Cl Turn

spinqualitylabelsall models 8ga3, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ga3 is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Ligands: CL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed CLCs are dimeric chloride channels and anion/proton exchangers that regulate processes such as muscle contraction and endo-lysosome acidification. Common gating controls their activity; its closure simultaneously silences both protomers, and its opening allows them to independently transport ions. Mutations affecting common gating in human CLCs cause dominant genetic disorders. The structural rearrangements underlying common gating are unknown. Here, using single-particle cryo-electron microscopy, we show that the prototypical Escherichia coli CLC-ec1 undergoes large-scale rearrangements in activating conditions. The slow, pH-dependent remodeling of the dimer interface leads to the concerted opening of the intracellular H(+) pathways and is required for transport. The more frequent formation of short water wires in the open H(+) pathway enables Cl(-) pore openings. Mutations at disease-causing sites favor CLC-ec1 activation and accelerate common gate opening in the human CLC-7 exchanger. We suggest that the pH activation mechanism of CLC-ec1 is related to the common gating of CLC-7. Structural basis of pH-dependent activation in a CLC transporter.,Fortea E, Lee S, Chadda R, Argyros Y, Sandal P, Mahoney-Kruszka R, Ciftci HD, Falzone ME, Huysmans G, Robertson JL, Boudker O, Accardi A Nat Struct Mol Biol. 2024 Apr;31(4):644-656. doi: 10.1038/s41594-023-01210-5. , Epub 2024 Jan 26. PMID:38279055 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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