Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-A resolution.
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.
Harrop
S J
SJ
Initiative for Biomolecular Structure, School of Physics and the Department of Medicine, University of New South Wales, New South Wales 2052, Australia.
DeMaere
M Z
MZ
Fairlie
W D
WD
Reztsova
T
T
Valenzuela
S M
SM
Mazzanti
M
M
Tonini
R
R
Qiu
M R
MR
Jankova
L
L
Warton
K
K
Bauskin
A R
AR
Wu
W M
WM
Pankhurst
S
S
Campbell
T J
TJ
Breit
S N
SN
Curmi
P M
PM
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
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