| Structural highlights
2r4v is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Related: | 2r5g |
| Gene: | CLIC2 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[CLIC2_HUMAN] Note=Defects in CLIC2 are a cause of a mental retardation with cardiopathy and seizures. Cardiac features include atrial fibrillation, cardiomegaly, and congestive heart failure.
Function
[CLIC2_HUMAN] Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Modulates the activity of RYR2 and inhibits calcium influx.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Board PG, Coggan M, Watson S, Gage PW, Dulhunty AF. CLIC-2 modulates cardiac ryanodine receptor Ca2+ release channels. Int J Biochem Cell Biol. 2004 Aug;36(8):1599-612. PMID:15147738 doi:10.1016/j.biocel.2004.01.026
- ↑ Dulhunty AF, Pouliquin P, Coggan M, Gage PW, Board PG. A recently identified member of the glutathione transferase structural family modifies cardiac RyR2 substate activity, coupled gating and activation by Ca2+ and ATP. Biochem J. 2005 Aug 15;390(Pt 1):333-43. PMID:15916532 doi:BJ20042113
- ↑ 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. Structure of the Janus protein human CLIC2. J Mol Biol. 2007 Nov 30;374(3):719-31. Epub 2007 Sep 20. PMID:17945253 doi:http://dx.doi.org/10.1016/j.jmb.2007.09.041
- ↑ 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. Structure of the Janus protein human CLIC2. J Mol Biol. 2007 Nov 30;374(3):719-31. Epub 2007 Sep 20. PMID:17945253 doi:http://dx.doi.org/10.1016/j.jmb.2007.09.041
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