4mqx | pdb_00004mqx
CLC-ec1 Fab Complex Cysless A399C-A432C mutant
Structural highlights
Function[CLCA_ECOLI] Proton-coupled chloride transporter. Functions as antiport system and exchanges two chloride ions for 1 proton. Probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response.[1] [2] [3] [4] [5] Publication Abstract from PubMedCLC-type exchangers mediate transmembrane Cl(-) transport. Mutations altering their gating properties cause numerous genetic disorders. However, their transport mechanism remains poorly understood. In conventional models, two gates alternatively expose substrates to the intra- or extracellular solutions. A glutamate was identified as the only gate in the CLCs, suggesting that CLCs function by a nonconventional mechanism. Here we show that transport in CLC-ec1, a prokaryotic homolog, is inhibited by cross-links constraining movement of helix O far from the transport pathway. Cross-linked CLC-ec1 adopts a wild-type-like structure, indicating stabilization of a native conformation. Movements of helix O are transduced to the ion pathway via a direct contact between its C terminus and a tyrosine that is a constitutive element of the second gate of CLC transporters. Therefore, the CLC exchangers have two gates that are coupled through conformational rearrangements outside the ion pathway. Conformational changes required for H(+)/Cl(-) exchange mediated by a CLC transporter.,Basilio D, Noack K, Picollo A, Accardi A Nat Struct Mol Biol. 2014 May;21(5):456-63. doi: 10.1038/nsmb.2814. Epub 2014 Apr, 20. PMID:24747941[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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