| Structural highlights
Function
CLIC1_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. Involved in regulation of the cell cycle.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
Chloride intracellular channel proteins exist in both a soluble cytosolic form and a membrane-bound form. The mechanism of conversion between the two forms is not properly understood, although one of the contributing factors is believed to be the variation in pH between the cytosol (~7.4) and the membrane (~5.5). We systematically mutated each of the three histidine residues in CLIC1 to an alanine at position 74 and a phenylalanine at positions 185 and 207. We examined the effect of the histidine-mediated pH dependence on the structure and global stability of CLIC1. None of the mutations were found to alter the global structure of the protein. However, the stability of H74A-CLIC1 and H185F-CLIC1, as calculated from the equilibrium unfolding data, is no longer dependent on pH because similar trends are observed at pH 7.0 and 5.5. The crystal structures show that the mutations result in changes in the local hydrogen bond coordination. Because the mutant total free energy change upon unfolding is not different from that of the wild type at pH 7.0, despite the presence of intermediates that are not seen in the wild type, we propose that it may be the stability of the intermediate state rather than the native state that is dependent on pH. On the basis of the lower stability of the intermediate in the H74A and H185F mutants compared to that of the wild type, we conclude that both His74 and His185 are involved in triggering the pH changes to the conformational stability of wild-type CLIC1 via their protonation, which stabilizes the intermediate state.
Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1.,Achilonu I, Fanucchi S, Cross M, Fernandes M, Dirr HW Biochemistry. 2012 Feb 7;51(5):995-1004. Epub 2012 Jan 23. PMID:22242893[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Valenzuela SM, Martin DK, Por SB, Robbins JM, Warton K, Bootcov MR, Schofield PR, Campbell TJ, Breit SN. Molecular cloning and expression of a chloride ion channel of cell nuclei. J Biol Chem. 1997 May 9;272(19):12575-82. PMID:9139710
- ↑ Tonini R, Ferroni A, Valenzuela SM, Warton K, Campbell TJ, Breit SN, Mazzanti M. Functional characterization of the NCC27 nuclear protein in stable transfected CHO-K1 cells. FASEB J. 2000 Jun;14(9):1171-8. PMID:10834939
- ↑ Valenzuela SM, Mazzanti M, Tonini R, Qiu MR, Warton K, Musgrove EA, Campbell TJ, Breit SN. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. J Physiol. 2000 Dec 15;529 Pt 3:541-52. PMID:11195932
- ↑ Tulk BM, Kapadia S, Edwards JC. CLIC1 inserts from the aqueous phase into phospholipid membranes, where it functions as an anion channel. Am J Physiol Cell Physiol. 2002 May;282(5):C1103-12. PMID:11940526 doi:10.1152/ajpcell.00402.2001
- ↑ Warton K, Tonini R, Fairlie WD, Matthews JM, Valenzuela SM, Qiu MR, Wu WM, Pankhurst S, Bauskin AR, Harrop SJ, Campbell TJ, Curmi PM, Breit SN, Mazzanti M. Recombinant CLIC1 (NCC27) assembles in lipid bilayers via a pH-dependent two-state process to form chloride ion channels with identical characteristics to those observed in Chinese hamster ovary cells expressing CLIC1. J Biol Chem. 2002 Jul 19;277(29):26003-11. Epub 2002 Apr 26. PMID:11978800 doi:http://dx.doi.org/10.1074/jbc.M203666200
- ↑ Harrop SJ, DeMaere MZ, Fairlie WD, Reztsova T, Valenzuela SM, Mazzanti M, Tonini R, Qiu MR, Jankova L, Warton K, Bauskin AR, Wu WM, Pankhurst S, Campbell TJ, Breit SN, Curmi PM. Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-A resolution. J Biol Chem. 2001 Nov 30;276(48):44993-5000. Epub 2001 Sep 10. PMID:11551966 doi:10.1074/jbc.M107804200
- ↑ Littler DR, Harrop SJ, Fairlie WD, Brown LJ, Pankhurst GJ, Pankhurst S, DeMaere MZ, Campbell TJ, Bauskin AR, Tonini R, Mazzanti M, Breit SN, Curmi PM. The intracellular chloride ion channel protein CLIC1 undergoes a redox-controlled structural transition. J Biol Chem. 2004 Mar 5;279(10):9298-305. Epub 2003 Nov 12. PMID:14613939 doi:http://dx.doi.org/10.1074/jbc.M308444200
- ↑ Achilonu I, Fanucchi S, Cross M, Fernandes M, Dirr HW. Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1. Biochemistry. 2012 Feb 7;51(5):995-1004. Epub 2012 Jan 23. PMID:22242893 doi:10.1021/bi201541w
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