Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-angstrom resolution

CLIC1 (NCC27) is a member of the highly conserved class of chloride ion cha nnels that exists in both soluble and integral membrane forms. Purified CLI C1 can integrate into synthetic lipid bilayers forming a chloride channel w ith similar properties to those observed in vivo. The structure of the solu ble form of CLIC1 has been determined at 1.4-Angstrom resolution. The prote in is monomeric and structurally homologous to the glutathione S-transferas e superfamily, and it has a redox-active site resembling glutaredoxin. The structure of the complex of CLIC1 with glutathione shows that glutathione o ccupies the redox-active site, which is adjacent to an open, elongated slot lined by basic residues. Integration of CLIC1 into the membrane is likely to require a major structural rearrangement, probably of the N-domain (resi dues 1-90), with the putative transmembrane helix arising from residues in the vicinity of the redox-active site. The structure indicates that CLIC1 i s likely to be controlled by redox-dependent processes.