2r4v

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Revision as of 10:16, 23 January 2008

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spinqualitylabelsall models 2r4v, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of human CLIC2, crystal form A

Overview

Chloride intracellular channel (CLIC) proteins possess the remarkable, property of being able to convert from a water-soluble state to a membrane, channel state. We determined the three-dimensional structure of human, CLIC2 in its water-soluble form by X-ray crystallography at 1.8-A, resolution from two crystal forms. In contrast to the previously, characterized CLIC1 protein, which forms a possibly functionally important, disulfide-induced dimer under oxidizing conditions, we show that CLIC2, possesses an intramolecular disulfide and that the protein remains, monomeric irrespective of redox conditions. Site-directed mutagenesis, studies show that removal of the intramolecular disulfide or introduction, of cysteine residues in CLIC2, equivalent to those that form the, intramolecular disulfide in CLIC1, does not cause dimer formation under, oxidizing conditions. We also show that CLIC2 forms pH-dependent chloride, channels in vitro with higher channel activity at low pH levels and that, the channels are subject to redox regulation. In both crystal forms, we, observed an extended loop region from the C-terminal domain, called the, foot loop, inserting itself into an interdomain crevice of a neighboring, molecule. The equivalent region in the structurally related glutathione, transferase superfamily corresponds to the active site. This so-called, foot-in-mouth interaction suggests that CLIC2 might recognize other, proteins such as the ryanodine receptor through a similar interaction.

About this Structure

2R4V is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Structure of the Janus Protein Human CLIC2., Cromer BA, Gorman MA, Hansen G, Adams JJ, Coggan M, Littler DR, Brown LJ, Mazzanti M, Breit SN, Curmi PM, Dulhunty AF, Board PG, Parker MW, J Mol Biol. 2007 Nov 30;374(3):719-31. Epub 2007 Sep 20. PMID:17945253

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