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-Structure paper
タイトル | Structural basis of pH-dependent activation in a CLC transporter. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 31, Issue 4, Page 644-656, Year 2024 |
掲載日 | 2024年1月26日 |
著者 | Eva Fortea / Sangyun Lee / Rahul Chadda / Yiorgos Argyros / Priyanka Sandal / Robyn Mahoney-Kruszka / Hatice Didar Ciftci / Maria E Falzone / Gerard Huysmans / Janice L Robertson / Olga Boudker / Alessio Accardi / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:38279055 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.6 - 3.5 Å |
構造データ | EMDB-29883, PDB-8ga0: EMDB-29884, PDB-8ga1: EMDB-29885, PDB-8ga3: EMDB-29890, PDB-8ga5: EMDB-29899, PDB-8gah: |
化合物 | ChemComp-CL: ChemComp-HOH: |
由来 |
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キーワード | TRANSPORT PROTEIN / CLC-ec1 / ecCLC / eriC / CLC transporter / chloride proton antiporter |