1RK4

Crystal Structure of a Soluble Dimeric Form of Oxidised CLIC1

Summary for 1RK4

• Entry DOI: 10.2210/pdb1rk4/pdb
• Related: 1K0M
• Descriptor: CHLORIDE INTRACELLULAR CHANNEL PROTEIN 1 (2 entities in total)
• Functional Keywords: glutathione-s-tranferase superfamily; chloride ion channel; redox-controlled structural transition, ion transport-membrane protein complex, ion transport/membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O00299
• Total number of polymer chains: 2
• Total formula weight: 54193.63

Authors

Littler, D.R.,Harrop, S.J.,Fairlie, W.D.,Brown, L.J.,Pankhurst, G.J.,Pankhurst, S.,DeMaere, M.Z.,Campbell, T.J.,Bauskin, A.R.,Tonini, R.,Mazzanti, M.,Breit, S.N.,Curmi, P.M. (deposition date: 2003-11-20, release date: 2003-12-02, Last modification date: 2024-11-20)

Primary citation

Littler, D.R.,Harrop, S.J.,Fairlie, W.D.,Brown, L.J.,Pankhurst, G.J.,Pankhurst, S.,DeMaere, M.Z.,Campbell, T.J.,Bauskin, A.R.,Tonini, R.,Mazzanti, M.,Breit, S.N.,Curmi, P.M.
The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition
J.Biol.Chem., 279:9298-9305, 2004

PubMed Abstract: Most proteins adopt a well defined three-dimensional structure; however, it is increasingly recognized that some proteins can exist with at least two stable conformations. Recently, a class of intracellular chloride ion channel proteins (CLICs) has been shown to exist in both soluble and integral membrane forms. The structure of the soluble form of CLIC1 is typical of a soluble glutathione S-transferase superfamily protein but contains a glutaredoxin-like active site. In this study we show that on oxidation CLIC1 undergoes a reversible transition from a monomeric to a non-covalent dimeric state due to the formation of an intramolecular disulfide bond (Cys-24-Cys-59). We have determined the crystal structure of this oxidized state and show that a major structural transition has occurred, exposing a large hydrophobic surface, which forms the dimer interface. The oxidized CLIC1 dimer maintains its ability to form chloride ion channels in artificial bilayers and vesicles, whereas a reducing environment prevents the formation of ion channels by CLIC1. Mutational studies show that both Cys-24 and Cys-59 are required for channel activity.

PubMed: 14613939
DOI: 10.1074/jbc.M308444200

Experimental method

X-RAY DIFFRACTION (1.792 Å)