title: Comparison of vertebrate and invertebrate CLIC proteins: the crystal structures of Caenorhabditis elegans EXC-4 and Drosophila melanogaster DmCLIC.
abstract: The crystal structures of two CLIC family members DmCLIC and EXC-4 from the invertebrates Drosophila melanogaster and Caenorhabditis elegans, respectively, have been determined. The proteins adopt a glutathione S-transferase (GST) fold. The structures are highly homologous to each other and more closely related to the known structures of the human CLIC1 and CLIC4 than to GSTs. The invertebrate CLICs show several unique features including an elongated C-terminal extension and a divalent metal binding site. The latter appears to alter the ancestral glutathione binding site, and thus, the invertebrate CLICs are unlikely to bind glutathione in the same manner as the GST proteins. Purified recombinant DmCLIC and EXC-4 both bind to lipid bilayers and can form ion channels in artificial lipid bilayers, albeit at low pH. EXC-4 differs from other CLIC proteins in that the conserved redox-active cysteine at the N-terminus of helix 1 is replaced by an aspartic acid residue. Other key distinguishing features of EXC-4 include the fact that it binds to artificial bilayers at neutral pH and this binding is not sensitive to oxidation. These differences with other CLIC family members are likely to be due to the substitution of the conserved cysteine by aspartic acid.
authors.affiliation: School of Physics, University of New South Wales, New South Wales 2052, Australia.
authors.forename: Dene R
authors.initials: DR
authors.lastname: Littler
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Harrop
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Brown
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Pankhurst
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Mynott
authors.forename: Paolo
authors.initials: P
authors.lastname: Luciani
authors.forename: Ramya A
authors.initials: RA
authors.lastname: Mandyam
authors.forename: Michele
authors.initials: M
authors.lastname: Mazzanti
authors.forename: Soichi
authors.initials: S
authors.lastname: Tanda
authors.forename: Mark A
authors.initials: MA
authors.lastname: Berryman
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: Paul M G
authors.initials: PM
authors.lastname: Curmi
mesh_terms: D000818:Animals; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry*; D002413:Cations, Divalent; D018118:Chloride Channels / Q000737:chemistry*; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster / Q000737:chemistry; D005978:Glutathione; D008051:Lipid Bilayers; D008670:Metals; D017434:Protein Structure, Tertiary
chemical_list: C527644:CLIC protein, Drosophila; D029742:Caenorhabditis elegans Proteins; D002413:Cations, Divalent; D018118:Chloride Channels; D029721:Drosophila Proteins; C480086:EXC-4 protein, C elegans; D008051:Lipid Bilayers; D008670:Metals; D005978:Glutathione