PDBsum entry 2ahe

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protein links
Metal transport PDB id
Protein chain
228 a.a. *
Waters ×196
* Residue conservation analysis
PDB id:
Name: Metal transport
Title: Crystal structure of a soluble form of clic4. Intercellular chloride ion channel
Structure: Chloride intracellular channel protein 4. Chain: a. Synonym: intracellular chloride ion channel protein p64h1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.80Å     R-factor:   0.196     R-free:   0.229
Authors: D.R.Littler,N.N.Assaad,S.J.Harrop,L.J.Brown,G.J.Pankhurst, P.Luciani,M.-I.Aguilar,M.Mazzanti,M.A.Berryman,S.N.Breit, P.M.G.Curmi
Key ref:
D.R.Littler et al. (2005). Crystal structure of the soluble form of the redox-regulated chloride ion channel protein CLIC4. FEBS J, 272, 4996-5007. PubMed id: 16176272 DOI: 10.1111/j.1742-4658.2005.04909.x
28-Jul-05     Release date:   16-Aug-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9Y696  (CLIC4_HUMAN) -  Chloride intracellular channel protein 4
253 a.a.
228 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   25 terms 
  Biological process     retina vasculature morphogenesis in camera-type eye   19 terms 
  Biochemical function     protein binding     4 terms  


DOI no: 10.1111/j.1742-4658.2005.04909.x FEBS J 272:4996-5007 (2005)
PubMed id: 16176272  
Crystal structure of the soluble form of the redox-regulated chloride ion channel protein CLIC4.
D.R.Littler, N.N.Assaad, S.J.Harrop, L.J.Brown, G.J.Pankhurst, P.Luciani, M.I.Aguilar, M.Mazzanti, M.A.Berryman, S.N.Breit, P.M.Curmi.
The structure of CLIC4, a member of the CLIC family of putative intracellular chloride ion channel proteins, has been determined at 1.8 Angstroms resolution by X-ray crystallography. The protein is monomeric and it is structurally similar to CLIC1, belonging to the GST fold class. Differences between the structures of CLIC1 and CLIC4 are localized to helix 2 in the glutaredoxin-like N-terminal domain, which has previously been shown to undergo a dramatic structural change in CLIC1 upon oxidation. The structural differences in this region correlate with the sequence differences, where the CLIC1 sequence appears to be atypical of the family. Purified, recombinant, wild-type CLIC4 is shown to bind to artificial lipid bilayers, induce a chloride efflux current when associated with artificial liposomes and produce an ion channel in artificial bilayers with a conductance of 30 pS. Membrane binding is enhanced by oxidation of CLIC4 while no channels were observed via tip-dip electrophysiology in the presence of a reducing agent. Thus, recombinant CLIC4 appears to be able to form a redox-regulated ion channel in the absence of any partner proteins.
  Selected figure(s)  
Figure 1.
Fig. 1. Overall crystal structure of CLIC4. (A) Ribbon diagram showing the crystal structure of CLIC4(ext), where the last two residues of the wild-type CLIC4 sequence have been replaced by a 16 residue peptide (top left hand corner). (B) The structure of CLIC1 in the same orientation as CLIC4 in (A). (C) A stereogram showing the C[ ]trace of CLIC4 with every 10th residue numbered. (D) A stereogram showing a superposition of the backbone traces of CLIC4 (green) and CLIC1 (mauve).
Figure 2.
Fig. 2. Detailed views of the CLIC4 structure. (A) Arg176 locks the two ends of the foot loop into place via a network of hydrogen bonds centered on it side chain guanidinium group. (B) The NLS of CLIC4 situated at the C-terminus of helix 6 and the subsequence loop. (C) Side chains in CLIC4 and CLIC1 adopt equivalent rotamers. Here Trp218 (CLIC4) and His208 (CLIC1) each stabilize the loop connecting helices 6 and 7 by forming equivalent hydrogen bonds to backbone carbonyl groups. (D) An overlay of the loop connecting helix 2 to -strand 3 from CLIC4 (green and red) and CLIC1 (atomic colors). All parts of this figure are in stereo.
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS J (2005, 272, 4996-5007) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21323602 A.F.Dulhunty, R.Hewawasam, D.Liu, M.G.Casarotto, and P.G.Board (2011).
Regulation of the cardiac muscle ryanodine receptor by glutathione transferases.
  Drug Metab Rev, 43, 236-252.  
20934451 D.W.Song, J.G.Lee, H.S.Youn, S.H.Eom, and d.o. .H.Kim (2011).
Ryanodine receptor assembly: A novel systems biology approach to 3D mapping.
  Prog Biophys Mol Biol, 105, 145-161.  
  20617112 A.Shukla, and S.H.Yuspa (2010).
CLIC4 and Schnurri-2: A dynamic duo in TGF-beta signaling with broader implications in cellular homeostasis and disease.
  Nucleus, 1, 144-149.  
20664558 B.A.Pierchala, M.R.Muñoz, and C.C.Tsui (2010).
Proteomic analysis of the slit diaphragm complex: CLIC5 is a protein critical for podocyte morphology and function.
  Kidney Int, 78, 868-882.  
20564201 F.N.Li, J.D.Yin, J.J.Ni, L.Liu, H.Y.Zhang, and M.Du (2010).
Chloride intracellular channel 5 modulates adipocyte accumulation in skeletal muscle by inhibiting preadipocyte differentiation.
  J Cell Biochem, 110, 1013-1021.  
  21040583 J.J.Tung, and J.Kitajewski (2010).
Chloride intracellular channel 1 functions in endothelial cell growth and migration.
  J Angiogenes Res, 2, 23.  
20610659 J.Z.Chuang, S.Y.Chou, and C.H.Sung (2010).
Chloride intracellular channel 4 is critical for the epithelial morphogenesis of RPE cells and retinal attachment.
  Mol Biol Cell, 21, 3017-3028.  
19448624 A.Shukla, M.Malik, C.Cataisson, Y.Ho, T.Friesen, K.S.Suh, and S.H.Yuspa (2009).
TGF-beta signalling is regulated by Schnurri-2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3.
  Nat Cell Biol, 11, 777-784.  
19776349 B.Ponsioen, L.van Zeijl, M.Langeslag, M.Berryman, D.Littler, K.Jalink, and W.H.Moolenaar (2009).
Spatiotemporal regulation of chloride intracellular channel protein CLIC4 by RhoA.
  Mol Biol Cell, 20, 4664-4672.  
19781102 Q.Yao, X.Qu, Q.Yang, D.A.Good, S.Dai, B.Kong, and M.Q.Wei (2009).
Blockage of transdifferentiation from fibroblast to myofibroblast in experimental ovarian cancer models.
  Mol Cancer, 8, 78.  
19650640 S.H.Stoychev, C.Nathaniel, S.Fanucchi, M.Brock, S.Li, K.Asmus, V.L.Woods, and H.W.Dirr (2009).
Structural dynamics of soluble chloride intracellular channel protein CLIC1 examined by amide hydrogen-deuterium exchange mass spectrometry.
  Biochemistry, 48, 8413-8421.  
19356589 X.Meng, G.Wang, C.Viero, Q.Wang, W.Mi, X.D.Su, T.Wagenknecht, A.J.Williams, Z.Liu, and C.C.Yin (2009).
CLIC2-RyR1 interaction and structural characterization by cryo-electron microscopy.
  J Mol Biol, 387, 320-334.  
17985355 D.R.Littler, S.J.Harrop, L.J.Brown, G.J.Pankhurst, A.V.Mynott, P.Luciani, R.A.Mandyam, M.Mazzanti, S.Tanda, M.A.Berryman, S.N.Breit, and P.M.Curmi (2008).
Comparison of vertebrate and invertebrate CLIC proteins: the crystal structures of Caenorhabditis elegans EXC-4 and Drosophila melanogaster DmCLIC.
  Proteins, 71, 364-378.
PDB codes: 2yv7 2yv9
18488014 E.Weerapana, G.M.Simon, and B.F.Cravatt (2008).
Disparate proteome reactivity profiles of carbon electrophiles.
  Nat Chem Biol, 4, 405-407.  
18186468 W.Mi, Y.H.Liang, L.Li, and X.D.Su (2008).
The crystal structure of human chloride intracellular channel protein 2: a disulfide bond with functional implications.
  Proteins, 71, 509-513.
PDB code: 2per
  18007051 B.A.Cromer, M.A.Gorman, G.Hansen, J.J.Adams, M.Coggan, P.G.Board, and M.W.Parker (2007).
Expression, purification, crystallization and preliminary X-ray diffraction analysis of chloride intracellular channel 2 (CLIC2).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 961-963.  
17380536 J.Adamkiewicz, K.Kaddatz, M.Rieck, B.Wilke, S.Müller-Brüsselbach, and R.Müller (2007).
Proteomic profile of mouse fibroblasts with a targeted disruption of the peroxisome proliferator activated receptor-beta/delta gene.
  Proteomics, 7, 1208-1216.  
17443730 K.S.Suh, M.Malik, A.Shukla, and S.H.Yuspa (2007).
CLIC4, skin homeostasis and cutaneous cancer: surprising connections.
  Mol Carcinog, 46, 599-604.  
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.