title: Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-A resolution.
abstract: CLIC1 (NCC27) is a member of the highly conserved class of chloride ion channels that exists in both soluble and integral membrane forms. Purified CLIC1 can integrate into synthetic lipid bilayers forming a chloride channel with similar properties to those observed in vivo. The structure of the soluble form of CLIC1 has been determined at 1.4-A resolution. The protein is monomeric and structurally homologous to the glutathione S-transferase superfamily, and it has a redox-active site resembling glutaredoxin. The structure of the complex of CLIC1 with glutathione shows that glutathione occupies 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 (residues 1-90), with the putative transmembrane helix arising from residues in the vicinity of the redox-active site. The structure indicates that CLIC1 is likely to be controlled by redox-dependent processes.
authors.affiliation: Initiative for Biomolecular Structure, School of Physics and the Department of Medicine, University of New South Wales, New South Wales 2052, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Harrop
authors.forename: M Z
authors.initials: MZ
authors.lastname: DeMaere
authors.forename: W D
authors.initials: WD
authors.lastname: Fairlie
authors.forename: T
authors.initials: T
authors.lastname: Reztsova
authors.forename: S M
authors.initials: SM
authors.lastname: Valenzuela
authors.forename: M
authors.initials: M
authors.lastname: Mazzanti
authors.forename: R
authors.initials: R
authors.lastname: Tonini
authors.forename: M R
authors.initials: MR
authors.lastname: Qiu
authors.forename: L
authors.initials: L
authors.lastname: Jankova
authors.forename: K
authors.initials: K
authors.lastname: Warton
authors.forename: A R
authors.initials: AR
authors.lastname: Bauskin
authors.forename: W M
authors.initials: WM
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Pankhurst
authors.forename: T J
authors.initials: TJ
authors.lastname: Campbell
authors.forename: S N
authors.initials: SN
authors.lastname: Breit
authors.forename: P M
authors.initials: PM
authors.lastname: Curmi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry* / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D004594:Electrophysiology; D004926:Escherichia coli / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: C501966:CLIC1 protein, human; D018118:Chloride Channels; D008051:Lipid Bilayers; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D002713:Chlorine; D005982:Glutathione Transferase; D005978:Glutathione; D003545:Cysteine