Crystal structure of Soluble Form Of CLIC4Crystal structure of Soluble Form Of CLIC4

Structural highlights

2d2z is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, RCSB, PDBsum

Function

[CLIC4_HUMAN] Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3. Has alternate cellular functions like a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. Could also promote endothelial cell proliferation and regulate endothelial morphogenesis (tubulogenesis).[1] [2] [3] [4] [5] [6]

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

The crystal structure of a wild type of the human soluble chloride intracellular ion channel CLIC4 (wCLIC4) has been determined at a resolution of 2.2A. The structure shows a homotrimer in an asymmetric unit, which is first observed in CLICs. The assembly of the trimer takes a unique triple interaction mode between three monomers with a hydrogen-bond network and hydrophobic contacts. Through such complicated interactions, the homotrimer of wCLIC4 is firmly stabilized. The structure shows an oligomeric mode with a unique assembly mechanism by which the oligomerization of CLIC4 can be performed without any intramolecular disulfide bond formation. It indicated a possibility that CLIC4 may take a unique structural organization distinct from CLIC1 for docking with lipid bilayers. In addition, the structure shows distinct conformational states of the h2 region for respective monomers of the trimer, which reveal an intrinsic conformational susceptibility for this significant region in the structural transition.

Trimeric structure of the wild soluble chloride intracellular ion channel CLIC4 observed in crystals.,Li Y, Li D, Zeng Z, Wang D Biochem Biophys Res Commun. 2006 May 19;343(4):1272-8. Epub 2006 Mar 27. PMID:16581025[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Ronnov-Jessen L, Villadsen R, Edwards JC, Petersen OW. Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts. Am J Pathol. 2002 Aug;161(2):471-80. PMID:12163372
  2. Berryman MA, Goldenring JR. CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells. Cell Motil Cytoskeleton. 2003 Nov;56(3):159-72. PMID:14569596 doi:http://dx.doi.org/10.1002/cm.10141
  3. Bohman S, Matsumoto T, Suh K, Dimberg A, Jakobsson L, Yuspa S, Claesson-Welsh L. Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis. J Biol Chem. 2005 Dec 23;280(51):42397-404. Epub 2005 Oct 20. PMID:16239224 doi:http://dx.doi.org/10.1074/jbc.M506724200
  4. Maeda K, Haraguchi M, Kuramasu A, Sato T, Ariake K, Sakagami H, Kondo H, Yanai K, Fukunaga K, Yanagisawa T, Sukegawa J. CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression. Biochem Biophys Res Commun. 2008 May 2;369(2):603-8. Epub 2008 Feb 25. PMID:18302930 doi:http://dx.doi.org/S0006-291X(08)00320-3
  5. Tung JJ, Hobert O, Berryman M, Kitajewski J. Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro. Angiogenesis. 2009;12(3):209-20. doi: 10.1007/s10456-009-9139-3. Epub 2009 Feb, 27. PMID:19247789 doi:http://dx.doi.org/10.1007/s10456-009-9139-3
  6. Littler DR, Assaad NN, Harrop SJ, Brown LJ, Pankhurst GJ, Luciani P, Aguilar MI, Mazzanti M, Berryman MA, Breit SN, Curmi PM. Crystal structure of the soluble form of the redox-regulated chloride ion channel protein CLIC4. FEBS J. 2005 Oct;272(19):4996-5007. PMID:16176272 doi:10.1111/j.1742-4658.2005.04909.x
  7. Li Y, Li D, Zeng Z, Wang D. Trimeric structure of the wild soluble chloride intracellular ion channel CLIC4 observed in crystals. Biochem Biophys Res Commun. 2006 May 19;343(4):1272-8. Epub 2006 Mar 27. PMID:16581025 doi:10.1016/j.bbrc.2006.03.099

2d2z, resolution 2.20Å

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