Cellular copper distribution: a mechanistic systems biology approach

Copper is an essential but potentially harmful trace element required in many enzymatic processes involving redox chemistry. Cellular copper homeostasis in mammals is predominantly maintained by regulating copper transport through the copper import CTR proteins and the copper exporters ATP7A and ATP7B. Once copper is imported into the cell, several pathways involving a number of copper proteins are responsible for trafficking it specifically where it is required for cellular life, thus avoiding the release of harmful free copper ions. In this study we review recent progress made in understanding the molecular mechanisms of copper transport in cells by analyzing structural features of copper proteins, their mode of interaction, and their thermodynamic and kinetic parameters, thus contributing to systems biology of copper within the cell.

[1]  J. Crapo,et al.  Molecular immunocytochemistry of the CuZn superoxide dismutase in rat hepatocytes , 1988, The Journal of cell biology.

[2]  N. Robinson,et al.  Chimeras of P1‐type ATPases and their transcriptional regulators: contributions of a cytosolic amino‐terminal domain to metal specificity , 2004, Molecular microbiology.

[3]  T. O’Halloran,et al.  Oxygen‐induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS , 2004, The EMBO journal.

[4]  Christos T. Chasapis,et al.  A NMR Study of the Interaction of a Three-domain Construct of ATP7A with Copper(I) and Copper(I)-HAH1 , 2005, Journal of Biological Chemistry.

[5]  F. Albert Cotton,et al.  Advanced Inorganic Chemistry , 1999 .

[6]  D. Winge,et al.  Yeast Contain a Non-proteinaceous Pool of Copper in the Mitochondrial Matrix* , 2004, Journal of Biological Chemistry.

[7]  D. Winge,et al.  Mapping the Functional Interaction of Sco1 and Cox2 in Cytochrome Oxidase Biogenesis* , 2008, Journal of Biological Chemistry.

[8]  C. Kozany,et al.  A Disulfide Relay System in the Intermembrane Space of Mitochondria that Mediates Protein Import , 2005, Cell.

[9]  I. Bertini,et al.  Human Sco1 functional studies and pathological implications of the P174L mutant , 2007, Proceedings of the National Academy of Sciences.

[10]  J. Herrmann,et al.  Catch me if you can! Oxidative protein trapping in the intermembrane space of mitochondria , 2007, The Journal of cell biology.

[11]  A. Rosato,et al.  The Atx1-Ccc2 complex is a metal-mediated protein-protein interaction , 2006, Nature chemical biology.

[12]  K. Pfeiffer,et al.  Supercomplexes in the respiratory chains of yeast and mammalian mitochondria , 2000, The EMBO journal.

[13]  B. Ludwig,et al.  Biogenesis of cytochrome c oxidase--in vitro approaches to study cofactor insertion into a bacterial subunit I. , 2008, Biochimica et biophysica acta.

[14]  D. Thiele,et al.  Biochemical and Genetic Analyses of Yeast and Human High Affinity Copper Transporters Suggest a Conserved Mechanism for Copper Uptake* , 2002, The Journal of Biological Chemistry.

[15]  G. Rödel,et al.  SCO1, a yeast nuclear gene essential for accumulation of mitochondrial cytochrome c oxidase subunit II , 1988, Molecular and General Genetics MGG.

[16]  I. Bertini,et al.  Characterization of the Binding Interface between the Copper Chaperone Atx1 and the First Cytosolic Domain of Ccc2 ATPase* 210 , 2001, The Journal of Biological Chemistry.

[17]  I. Voskoboinik,et al.  The Regulation of Catalytic Activity of the Menkes Copper-translocating P-type ATPase , 2001, The Journal of Biological Chemistry.

[18]  Deenah Osman,et al.  Copper homeostasis in bacteria. , 2008, Advances in applied microbiology.

[19]  D. Cox,et al.  Intracellular trafficking of the human Wilson protein: the role of the six N-terminal metal-binding sites. , 2004, The Biochemical journal.

[20]  B. Kemp,et al.  Phosphorylation regulates copper-responsive trafficking of the Menkes copper transporting P-type ATPase. , 2009, The international journal of biochemistry & cell biology.

[21]  W. Neupert,et al.  The disulfide relay system of mitochondria is required for the biogenesis of mitochondrial Ccs1 and Sod1. , 2009, Journal of molecular biology.

[22]  D. Glerum,et al.  Purification and Characterization of Yeast Sco1p, a Mitochondrial Copper Protein* , 2002, The Journal of Biological Chemistry.

[23]  Christos T. Chasapis,et al.  An NMR study of the interaction between the human copper(I) chaperone and the second and fifth metal‐binding domains of the Menkes protein , 2005, The FEBS journal.

[24]  A. Rosenzweig,et al.  Cu(I) Binding and Transfer by the N Terminus of the Wilson Disease Protein* , 2007, Journal of Biological Chemistry.

[25]  C. Toyoshima,et al.  Crystal structure of the calcium pump with a bound ATP analogue , 2004, Nature.

[26]  J. Kaplan,et al.  Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase reveal a copper cluster at a domain III dimer interface. , 2005, Biochemistry.

[27]  T. O’Halloran,et al.  Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. , 1999, Science.

[28]  F. Fontanesi,et al.  Suppression mechanisms of COX assembly defects in yeast and human: insights into the COX assembly process. , 2009, Biochimica et biophysica acta.

[29]  A. Tzagoloff,et al.  Characterization of COX19, a Widely Distributed Gene Required for Expression of Mitochondrial Cytochrome Oxidase* , 2002, The Journal of Biological Chemistry.

[30]  M. Harrison,et al.  Mechanisms for protection against copper toxicity. , 1998, The American journal of clinical nutrition.

[31]  R. Klausner,et al.  Molecular characterization of a copper transport protein in S. cerevisiae: An unexpected role for copper in iron transport , 1994, Cell.

[32]  M. Solioz,et al.  Copper homeostasis in Enterococcus hirae. , 1999, Advances in experimental medicine and biology.

[33]  N. Robinson,et al.  Understanding how cells allocate metals using metal sensors and metallochaperones. , 2005, Accounts of chemical research.

[34]  C. Toyoshima,et al.  Nucleotide recognition by CopA, a Cu+‐transporting P‐type ATPase , 2009, The EMBO journal.

[35]  I. Bertini,et al.  A Structural-Dynamical Characterization of Human Cox17* , 2008, Journal of Biological Chemistry.

[36]  A. Lamb,et al.  Heterodimeric structure of superoxide dismutase in complex with its metallochaperone , 2001, Nature Structural Biology.

[37]  Anthony P. Monaco,et al.  Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein , 1993, Nature Genetics.

[38]  Agustina Rodriguez-Granillo,et al.  Lysine-60 in copper chaperone Atox1 plays an essential role in adduct formation with a target Wilson disease domain. , 2009, Journal of the American Chemical Society.

[39]  D. Thiele,et al.  Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. , 2006, Cell metabolism.

[40]  A. G. Wedd,et al.  A C-terminal domain of the membrane copper pump Ctr1 exchanges copper(I) with the copper chaperone Atx1. , 2002, Chemical communications.

[41]  J. Markley,et al.  Solution structure of the N-domain of Wilson disease protein: distinct nucleotide-binding environment and effects of disease mutations. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[42]  I. Bertini,et al.  A structural characterization of human SCO2. , 2007, Structure.

[43]  S. Lutsenko,et al.  The Distinct Roles of the N-terminal Copper-binding Sites in Regulation of Catalytic Activity of the Wilson's Disease Protein* , 2003, Journal of Biological Chemistry.

[44]  P. Boyer,et al.  Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology , 2007, Proceedings of the National Academy of Sciences.

[45]  Essential Cys-Pro-Cys motif of Caenorhabditis elegans copper transport ATPase. , 1998, Bioscience, biotechnology, and biochemistry.

[46]  D. Price,et al.  The Copper Chaperone CCS Is Abundant in Neurons and Astrocytes in Human and Rodent Brain , 1999, Journal of neurochemistry.

[47]  D. Winge,et al.  Specific Copper Transfer from the Cox17 Metallochaperone to Both Sco1 and Cox11 in the Assembly of Yeast Cytochrome c Oxidase* , 2004, Journal of Biological Chemistry.

[48]  Antonio Rosato,et al.  Occurrence of copper proteins through the three domains of life: a bioinformatic approach. , 2008, Journal of proteome research.

[49]  T. O’Halloran,et al.  Amyotrophic Lateral Sclerosis Mutations Have the Greatest Destabilizing Effect on the Apo- and Reduced Form of SOD1, Leading to Unfolding and Oxidative Aggregation* , 2005, Journal of Biological Chemistry.

[50]  A. Rosato,et al.  The Binding Mode of ATP Revealed by the Solution Structure of the N-domain of Human ATP7A* , 2009, The Journal of Biological Chemistry.

[51]  C. Urbanke,et al.  Sulfate acts as phosphate analog on the monomeric catalytic fragment of the CPx-ATPase CopB from Sulfolobus solfataricus. , 2007, Journal of molecular biology.

[52]  A. Tiwari,et al.  Familial Amyotrophic Lateral Sclerosis Mutants of Copper/Zinc Superoxide Dismutase Are Susceptible to Disulfide Reduction* , 2003, The Journal of Biological Chemistry.

[53]  A. Rosenzweig,et al.  Structure of the actuator domain from the Archaeoglobus fulgidus Cu(+)-ATPase. , 2006, Biochemistry.

[54]  R. Klausner,et al.  The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake. , 1994, The Journal of biological chemistry.

[55]  M. Marahiel,et al.  Copper Acquisition Is Mediated by YcnJ and Regulated by YcnK and CsoR in Bacillus subtilis , 2009, Journal of bacteriology.

[56]  N. Pfanner,et al.  Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase , 2008, The Journal of cell biology.

[57]  L. T. Jensen,et al.  Activation of CuZn Superoxide Dismutases from Caenorhabditis elegans Does Not Require the Copper Chaperone CCS* , 2005, Journal of Biological Chemistry.

[58]  J. Mercer,et al.  Copper-induced trafficking of the Cu-ATPases: A key mechanism for copper homeostasis , 2003, Biometals.

[59]  E. Shoubridge,et al.  The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. , 2007, Cell metabolism.

[60]  D. Cox,et al.  The Wilson disease gene: spectrum of mutations and their consequences , 1995, Nature Genetics.

[61]  T. O’Halloran,et al.  Factors Controlling the Uptake of Yeast Copper/Zinc Superoxide Dismutase into Mitochondria* , 2003, Journal of Biological Chemistry.

[62]  D. Winge,et al.  “ Pulling the plug ” on cellular copper : The role of mitochondria in copper export , 2008 .

[63]  J. Mercer,et al.  Copper exposure induces trafficking of the menkes protein in intestinal epithelium of ATP7A transgenic mice. , 2005, The Journal of nutrition.

[64]  N. Capitanio,et al.  Cytochrome oxidase assembly in yeast requires the product of COX11, a homolog of the P. denitrificans protein encoded by ORF3. , 1990, The EMBO journal.

[65]  M. Nakano,et al.  Spectroscopic studies of metal binding and metal selectivity in Bacillus subtilis BSco, a Homologue of the Yeast Mitochondrial Protein Sco1p. , 2005, Journal of the American Chemical Society.

[66]  J. Valentine,et al.  Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[67]  A. Rosato,et al.  The Different Intermolecular Interactions of the Soluble Copper-binding Domains of the Menkes Protein, ATP7A* , 2007, Journal of Biological Chemistry.

[68]  J. Elliott,et al.  Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo , 2009, Neurobiology of Disease.

[69]  A. Rosato,et al.  An NMR Study of the Interaction of the N-terminal Cytoplasmic Tail of the Wilson Disease Protein with Copper(I)-HAH1* , 2009, Journal of Biological Chemistry.

[70]  I. Bertini,et al.  SOD1 and Amyotrophic Lateral Sclerosis: Mutations and Oligomerization , 2008, PloS one.

[71]  A. Rosato,et al.  Solution structures of the actuator domain of ATP7A and ATP7B, the Menkes and Wilson disease proteins. , 2009, Biochemistry.

[72]  M. Linder.  Biochemistry of Copper , 1991, Biochemistry of the Elements.

[73]  S. Lutsenko,et al.  X-ray Absorption Spectroscopy of the Copper Chaperone HAH1 Reveals a Linear Two-coordinate Cu(I) Center Capable of Adduct Formation with Exogenous Thiols and Phosphines* , 2003, Journal of Biological Chemistry.

[74]  B. Lai,et al.  Copper redistribution in Atox1-deficient mouse fibroblast cells , 2009, JBIC Journal of Biological Inorganic Chemistry.

[75]  I. Fridovich,et al.  Mitochondrial superoxide simutase. Site of synthesis and intramitochondrial localization. , 1973, The Journal of biological chemistry.

[76]  M. H. Barros,et al.  COX23, a Homologue of COX17, Is Required for Cytochrome Oxidase Assembly* , 2004, Journal of Biological Chemistry.

[77]  R. Casareno,et al.  The Copper Chaperone for Superoxide Dismutase* , 1997, The Journal of Biological Chemistry.

[78]  I. Bertini,et al.  Metallochaperones and metal-transporting ATPases: a comparative analysis of sequences and structures. , 2002, Genome research.

[79]  E. Shoubridge,et al.  Human SCO2 is required for the synthesis of CO II and as a thiol-disulphide oxidoreductase for SCO1. , 2009, Human molecular genetics.

[80]  D. Winge,et al.  Mitochondrial Matrix Copper Complex Used in Metallation of Cytochrome Oxidase and Superoxide Dismutase* , 2006, Journal of Biological Chemistry.

[81]  D. Winge,et al.  Metal-ion regulation of gene expression in yeast. , 1998, Current opinion in chemical biology.

[82]  T. Meyer,et al.  Oxidative switches in functioning of mammalian copper chaperone Cox17. , 2007, The Biochemical journal.

[83]  J. Argüello,et al.  Chaperone-mediated Cu+ Delivery to Cu+ Transport ATPases , 2009, The Journal of Biological Chemistry.

[84]  S. Kume,et al.  Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. , 1972, The Journal of biological chemistry.

[85]  E. Shoubridge,et al.  A hemizygous SCO2 mutation in an early onset rapidly progressive, fatal cardiomyopathy. , 2006, Molecular genetics and metabolism.

[86]  P. Rich,et al.  Two Menkes-type ATPases Supply Copper for Photosynthesis inSynechocystis PCC 6803* , 2001, The Journal of Biological Chemistry.

[87]  Ivano Bertini,et al.  Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer , 2008, Proceedings of the National Academy of Sciences.

[88]  Hiromi Nomura,et al.  Structural changes in the calcium pump accompanying the dissociation of calcium , 2002, Nature.

[89]  S. Aller,et al.  A structural perspective on copper uptake in eukaryotes , 2007, BioMetals.

[90]  D. Glerum,et al.  SCO1 and SCO2 Act as High Copy Suppressors of a Mitochondrial Copper Recruitment Defect in Saccharomyces cerevisiae* , 1996, The Journal of Biological Chemistry.

[91]  N. Taniguchi,et al.  A pivotal role of Zn-binding residues in the function of the copper chaperone for SOD1. , 2000, Biochemical and biophysical research communications.

[92]  G. Veglia,et al.  Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease , 2005, Proteins.

[93]  Z. Jia,et al.  Identification of a disulfide switch in BsSco, a member of the Sco family of cytochrome c oxidase assembly proteins. , 2005, Biochemistry.

[94]  J. Kaplan,et al.  Cell‐Specific Trafficking Suggests a new role for Renal ATP7B in the Intracellular Copper Storage , 2009, Traffic.

[95]  A. Rosato,et al.  Solution structure and backbone dynamics of the Cu(I) and apo forms of the second metal-binding domain of the Menkes protein ATP7A. , 2004, Biochemistry.

[96]  J. Abrahams,et al.  ATP-induced conformational changes of the nucleotide-binding domain of Na,K-ATPase , 2003, Nature Structural Biology.

[97]  I. Bertini,et al.  Structure and Properties of Copper-Zinc Superoxide Dismutases , 1998 .

[98]  L. Banci,et al.  The copper-responsive repressor CopR of Lactococcus lactis is a 'winged helix' protein. , 2009, The Biochemical journal.

[99]  A. Lamb,et al.  Heterodimer formation between superoxide dismutase and its copper chaperone. , 2000, Biochemistry.

[100]  T. Umahara,et al.  Cu Zn superoxide dismutase-like immunoreactivity in Lewy body-like inclusions of sporadic amyotrophic lateral sclerosis , 1994, Neuroscience Letters.

[101]  A. McEwan,et al.  PrrC from Rhodobacter sphaeroides, a homologue of eukaryotic Sco proteins, is a copper‐binding protein and may have a thiol‐disulfide oxidoreductase activity , 2002, FEBS letters.

[102]  I. Bertini,et al.  Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[103]  I. Bertini,et al.  The delivery of copper for thylakoid import observed by NMR. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[104]  T. Tomizaki,et al.  Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A , 1995, Science.

[105]  I. Fridovich,et al.  Examination of the role of arginine-143 in the human copper and zinc superoxide dismutase by site-specific mutagenesis. , 1987, The Journal of biological chemistry.

[106]  D. Winge,et al.  The mitochondrial copper metallochaperone Cox17 exists as an oligomeric, polycopper complex. , 2001, Biochemistry.

[107]  A. Rosato,et al.  Solution structure of the apo and copper(I)-loaded human metallochaperone HAH1. , 2004, Biochemistry.

[108]  M Bolognesi,et al.  Conserved patterns in the Cu,Zn superoxide dismutase family. , 1994, Journal of molecular biology.

[109]  J. Argüello,et al.  Mechanism of Cu+-transporting ATPases: Soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites , 2008, Proceedings of the National Academy of Sciences.

[110]  I. Bertini,et al.  Solution Structures of a Cyanobacterial Metallochaperone , 2004, Journal of Biological Chemistry.

[111]  Jennifer Stine Elam,et al.  Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS , 2003, Nature Structural Biology.

[112]  J. Mercer,et al.  Copper binding to the N-terminal metal-binding sites or the CPC motif is not essential for copper-induced trafficking of the human Wilson protein (ATP7B). , 2007, The Biochemical journal.

[113]  Agathe Urvoas,et al.  Copper-mediated homo-dimerisation for the HAH1 metallochaperone. , 2004, Biochemical and biophysical research communications.

[114]  H. Kawamata,et al.  Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria. , 2008, Human molecular genetics.

[115]  A. Munnich,et al.  Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. , 2000, American journal of human genetics.

[116]  D. Winge,et al.  Functional Analysis of the Domains in Cox11* , 2005, Journal of Biological Chemistry.

[117]  Oksana Gavrilova,et al.  p53 Regulates Mitochondrial Respiration , 2006, Science.

[118]  I. Bertini,et al.  Metal-free superoxide dismutase forms soluble oligomers under physiological conditions: A possible general mechanism for familial ALS , 2007, Proceedings of the National Academy of Sciences.

[119]  T. O’Halloran,et al.  Mechanism of Cu,Zn-Superoxide Dismutase Activation by the Human Metallochaperone hCCS * , 2001, The Journal of Biological Chemistry.

[120]  M. Di Valentin,et al.  Cox11p Is Required for Stable Formation of the CuBand Magnesium Centers of Cytochrome c Oxidase* , 2000, The Journal of Biological Chemistry.

[121]  L. T. Jensen,et al.  A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. , 2001, The Journal of biological chemistry.

[122]  D. Winge,et al.  Metalloregulation of FRE1 and FRE2Homologs in Saccharomyces cerevisiae * , 1998, The Journal of Biological Chemistry.

[123]  K. Axelsen,et al.  Evolution of Substrate Specificities in the P-Type ATPase Superfamily , 1998, Journal of Molecular Evolution.

[124]  M. Saier,et al.  Bioinformatic Characterization of P-Type ATPases Encoded Within the Fully Sequenced Genomes of 26 Eukaryotes , 2009, Journal of Membrane Biology.

[125]  Christopher J. De Feo,et al.  Three-dimensional structure of the human copper transporter hCTR1 , 2009, Proceedings of the National Academy of Sciences.

[126]  A. Rosato,et al.  The functions of Sco proteins from genome-based analysis. , 2007, Journal of proteome research.

[127]  G. Rödel,et al.  Evidence for the association of yeast mitochondrial ribosomes with Cox11p, a protein required for the CuB site formation of cytochrome c oxidase , 2005, Current Genetics.

[128]  I. Bertini,et al.  The Unusually Stable Quaternary Structure of Human Cu,Zn-Superoxide Dismutase 1 Is Controlled by Both Metal Occupancy and Disulfide Status* , 2004, Journal of Biological Chemistry.

[129]  E. Shoubridge,et al.  Human Sco1 and Sco2 Function as Copper-binding Proteins* , 2005, Journal of Biological Chemistry.

[130]  P. Rich,et al.  A Copper Metallochaperone for Photosynthesis and Respiration Reveals Metal-specific Targets, Interaction with an Importer, and Alternative Sites for Copper Acquisition* , 2002, The Journal of Biological Chemistry.

[131]  D. Thiele,et al.  Biochemical Characterization of the Human Copper Transporter Ctr1* , 2002, The Journal of Biological Chemistry.

[132]  I. Bertini,et al.  Solution Structure of Cox11, a Novel Type of β-Immunoglobulin-like Fold Involved in CuB Site Formation of Cytochrome c Oxidase* , 2004, Journal of Biological Chemistry.

[133]  Ivano Bertini,et al.  A copper(I) protein possibly involved in the assembly of CuA center of bacterial cytochrome c oxidase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[134]  Devis Sinani,et al.  Copper Transport Activity of Yeast Ctr1 Is Down-regulated via Its C Terminus in Response to Excess Copper* , 2009, Journal of Biological Chemistry.

[135]  V. Culotta,et al.  Copper Activation of Superoxide Dismutase 1 (SOD1) in Vivo , 2000, The Journal of Biological Chemistry.

[136]  Kevin M. Clark,et al.  Selenocysteine positional variants reveal contributions to copper binding from cysteine residues in domains 2 and 3 of human copper chaperone for superoxide dismutase. , 2008, Biochemistry.

[137]  D. Winge,et al.  Yeast Sco1, a Protein Essential for Cytochrome cOxidase Function Is a Cu(I)-binding Protein* , 2001, The Journal of Biological Chemistry.

[138]  T. O’Halloran,et al.  Posttranslational modifications in Cu,Zn-superoxide dismutase and mutations associated with amyotrophic lateral sclerosis. , 2006, Antioxidants & redox signaling.

[139]  P. Hart,et al.  Activation of Cu,Zn-Superoxide Dismutase in the Absence of Oxygen and the Copper Chaperone CCS* , 2009, The Journal of Biological Chemistry.

[140]  I. Bertini,et al.  Solution Structure of the Yeast Copper Transporter Domain Ccc2a in the Apo and Cu(I)-loaded States* , 2001, The Journal of Biological Chemistry.

[141]  D. Winge,et al.  Yeast Cox11, a Protein Essential for Cytochrome cOxidase Assembly, Is a Cu(I)-binding Protein* , 2002, The Journal of Biological Chemistry.

[142]  N. Pfanner,et al.  Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins , 2004, The EMBO journal.

[143]  K. Tokatlidis,et al.  Mitochondrial ATP‐independent chaperones , 2009, IUBMB life.

[144]  Thomas V. O'Halloran,et al.  Metallochaperones, an Intracellular Shuttle Service for Metal Ions* , 2000, The Journal of Biological Chemistry.

[145]  C. Toyoshima,et al.  Domain Organization and Movements in Heavy Metal Ion Pumps , 2007, Journal of Biological Chemistry.

[146]  B. Halliwell,et al.  Role of free radicals and catalytic metal ions in human disease: an overview. , 1990, Methods in enzymology.

[147]  B. Hill,et al.  Characterization of YpmQ, an Accessory Protein Required for the Expression of Cytochrome c Oxidase in Bacillus subtilis * , 2000, The Journal of Biological Chemistry.

[148]  S. Lutsenko,et al.  The Lys1010–Lys1325 Fragment of the Wilson's Disease Protein Binds Nucleotides and Interacts with the N-terminal Domain of This Protein in a Copper-dependent Manner* , 2001, The Journal of Biological Chemistry.

[149]  Rajendra Pilankatta,et al.  High Yield Heterologous Expression of Wild-type and Mutant Cu+-ATPase (ATP7B, Wilson Disease Protein) for Functional Characterization of Catalytic Activity and Serine Residues Undergoing Copper-dependent Phosphorylation , 2009, The Journal of Biological Chemistry.

[150]  R. Portmann,et al.  Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking , 2009, BioMetals.

[151]  L. T. Hall,et al.  X-ray crystallographic and analytical ultracentrifugation analyses of truncated and full-length yeast copper chaperones for SOD (LYS7): a dimer-dimer model of LYS7-SOD association and copper delivery. , 2000, Biochemistry.

[152]  K. Davies,et al.  Mitochondrial free radical generation, oxidative stress, and aging. , 2000, Free radical biology & medicine.

[153]  I. Bertini,et al.  Structural Basis for the Function of the N-terminal Domain of the ATPase CopA from Bacillus subtilis* , 2003, Journal of Biological Chemistry.

[154]  N. Blackburn,et al.  A multinuclear copper(I) cluster forms the dimerization interface in copper-loaded human copper chaperone for superoxide dismutase. , 2007, Biochemistry.

[155]  D. Winge,et al.  Cox17 Is Functional When Tethered to the Mitochondrial Inner Membrane* , 2004, Journal of Biological Chemistry.

[156]  E. Shoubridge,et al.  Cytochrome c Oxidase Deficiency , 1990, Pediatric Research.

[157]  N. Robinson,et al.  Zn, Cu and Co in cyanobacteria: selective control of metal availability. , 2003, FEMS microbiology reviews.

[158]  D W Cox,et al.  Role of the Copper-binding Domain in the Copper Transport Function of ATP7B, the P-type ATPase Defective in Wilson Disease* , 1999, The Journal of Biological Chemistry.

[159]  I. Voskoboinik,et al.  Copper-regulated Trafficking of the Menkes Disease Copper ATPase Is Associated with Formation of a Phosphorylated Catalytic Intermediate* , 2002, The Journal of Biological Chemistry.

[160]  T. Stemmler,et al.  Structure of the Two Transmembrane Cu+ Transport Sites of the Cu+-ATPases* , 2008, Journal of Biological Chemistry.

[161]  I. Bertini,et al.  NMR structural analysis of the soluble domain of ZiaA-ATPase and the basis of selective interactions with copper metallochaperone Atx1 , 2009, JBIC Journal of Biological Inorganic Chemistry.

[162]  R. Klausner,et al.  Identification and Functional Expression of HAH1, a Novel Human Gene Involved in Copper Homeostasis* , 1997, The Journal of Biological Chemistry.

[163]  T. O’Halloran,et al.  Multiple Protein Domains Contribute to the Action of the Copper Chaperone for Superoxide Dismutase* , 1999, The Journal of Biological Chemistry.

[164]  D. Winge,et al.  Characterization of the Cytochrome c Oxidase Assembly Factor Cox19 of Saccharomyces cerevisiae* , 2007, Journal of Biological Chemistry.

[165]  D. Rees,et al.  A P-type ATPase importer that discriminates between essential and toxic transition metals , 2009, Proceedings of the National Academy of Sciences.

[166]  D. Sideris,et al.  Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. , 2005, Journal of molecular biology.

[167]  Amy C Rosenzweig,et al.  Structure of the ATP Binding Domain from the Archaeoglobus fulgidus Cu+-ATPase* , 2006, Journal of Biological Chemistry.

[168]  Nikolay V Dokholyan,et al.  The rate and equilibrium constants for a multistep reaction sequence for the aggregation of superoxide dismutase in amyotrophic lateral sclerosis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[169]  R. Albers.  Biochemical aspects of active transport. , 1967, Annual review of biochemistry.

[170]  I. Bertini,et al.  Structural and dynamic aspects related to oligomerization of apo SOD1 and its mutants , 2009, Proceedings of the National Academy of Sciences.

[171]  Antonio Rosato,et al.  Copper(I)-mediated protein-protein interactions result from suboptimal interaction surfaces. , 2009, The Biochemical journal.

[172]  D. Glerum,et al.  Characterization of COX17, a Yeast Gene Involved in Copper Metabolism and Assembly of Cytochrome Oxidase* , 1996, The Journal of Biological Chemistry.

[173]  A. Lode,et al.  Mitochondrial copper metabolism in yeast: interaction between Sco1p and Cox2p , 2000, FEBS letters.

[174]  Antonio Rosato,et al.  Role of the N-Terminal Tail of Metal-Transporting P1B-type ATPases from Genome-Wide Analysis and Molecular Dynamics Simulations , 2009, J. Chem. Inf. Model..

[175]  E. Shoubridge,et al.  Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. , 2004, Human molecular genetics.

[176]  R. Hassett,et al.  Evidence for Cu(II) Reduction as a Component of Copper Uptake by Saccharomyces cerevisiae(*) , 1995, The Journal of Biological Chemistry.

[177]  H. Kodama,et al.  Molecular genetics and pathophysiology of Menkes disease , 1999, Pediatrics international : official journal of the Japan Pediatric Society.

[178]  J. Gitlin,et al.  Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[179]  William I. Wood,et al.  Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase , 1998, Nature Structural Biology.

[180]  J. Valentine,et al.  Evidence for a Novel Role of Copper-Zinc Superoxide Dismutase in Zinc Metabolism* , 2001, The Journal of Biological Chemistry.

[181]  Ivano Bertini,et al.  Solution structure of Sco1: a thioredoxin-like protein Involved in cytochrome c oxidase assembly. , 2003, Structure.

[182]  L. Ellerby,et al.  Mutations in copper-zinc superoxide dismutase that cause amyotrophic lateral sclerosis alter the zinc binding site and the redox behavior of the protein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[183]  D. Winge,et al.  Isolated Cytochrome c Oxidase Deficiency in G93A SOD1 Mice Overexpressing CCS Protein* , 2008, Journal of Biological Chemistry.

[184]  J. Rommens,et al.  The Wilson disease gene is a putative copper transporting P–type ATPase similar to the Menkes gene , 1993, Nature Genetics.

[185]  P. Verhaert,et al.  Development of a generic approach to native metalloproteomics: application to the quantitative identification of soluble copper proteins in Escherichia coli , 2009, JBIC Journal of Biological Inorganic Chemistry.

[186]  A. Rosato,et al.  An atomic-level investigation of the disease-causing A629P mutant of the Menkes protein, ATP7A. , 2005, Journal of molecular biology.

[187]  G. Howlett,et al.  C-terminal domain of the membrane copper transporter Ctr1 from Saccharomyces cerevisiae binds four Cu(I) ions as a cuprous-thiolate polynuclear cluster: sub-femtomolar Cu(I) affinity of three proteins involved in copper trafficking. , 2004, Journal of the American Chemical Society.

[188]  D. Borchelt,et al.  A Limited Role for Disulfide Cross-linking in the Aggregation of Mutant SOD1 Linked to Familial Amyotrophic Lateral Sclerosis* , 2008, Journal of Biological Chemistry.

[189]  A. Barrientos,et al.  Mitochondrial copper metabolism and delivery to cytochrome c oxidase , 2008, IUBMB life.

[190]  Ivano Bertini,et al.  Modeling protein-protein complexes involved in the cytochrome C oxidase copper-delivery pathway. , 2007, Journal of proteome research.

[191]  Conrad Bessant,et al.  Protein-folding location can regulate manganese-binding versus copper- or zinc-binding , 2008, Nature.

[192]  S. Lutsenko,et al.  Cellular multitasking: the dual role of human Cu-ATPases in cofactor delivery and intracellular copper balance. , 2008, Archives of biochemistry and biophysics.

[193]  A. Vieyra,et al.  Cyclic AMP‐dependent protein kinase controls energy interconversion during the catalytic cycle of the yeast copper‐ATPase , 2008, FEBS letters.

[194]  D. Stokes,et al.  Structure of a copper pump suggests a regulatory role for its metal-binding domain. , 2008, Structure.

[195]  A. K. Mandal,et al.  Identification of the Transmembrane Metal Binding Site in Cu+-transporting PIB-type ATPases* , 2004, Journal of Biological Chemistry.

[196]  I. Bertini,et al.  A hint for the function of human Sco1 from different structures. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[197]  A. Craig,et al.  NMDA Receptor Activation Mediates Copper Homeostasis in Hippocampal Neurons , 2005, The Journal of Neuroscience.

[198]  T. Tomizaki,et al.  The Whole Structure of the 13-Subunit Oxidized Cytochrome c Oxidase at 2.8 Å , 1996, Science.

[199]  I. Bertini,et al.  MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria , 2009, Nature Structural &Molecular Biology.

[200]  M. Ushio-Fukai,et al.  Novel Role of Antioxidant-1 (Atox1) as a Copper-dependent Transcription Factor Involved in Cell Proliferation* , 2008, Journal of Biological Chemistry.

[201]  P. Sadler,et al.  A novel copper site in a cyanobacterial metallochaperone. , 2004, The Biochemical journal.

[202]  B. Lai,et al.  Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[203]  A. Chakrabartty,et al.  Oxidation-induced Misfolding and Aggregation of Superoxide Dismutase and Its Implications for Amyotrophic Lateral Sclerosis* , 2002, The Journal of Biological Chemistry.

[204]  W. Kühlbrandt.  Biology, structure and mechanism of P-type ATPases , 2004, Nature Reviews Molecular Cell Biology.

[205]  I. Fridovich,et al.  Subcellular Distribution of Superoxide Dismutases (SOD) in Rat Liver , 2001, The Journal of Biological Chemistry.

[206]  Torsten Herrmann,et al.  Solution Structure and Intermolecular Interactions of the Third Metal-binding Domain of ATP7A, the Menkes Disease Protein* , 2006, Journal of Biological Chemistry.

[207]  I. Bertini,et al.  Folding studies of Cox17 reveal an important interplay of cysteine oxidation and copper binding. , 2005, Structure.

[208]  I. Bertini,et al.  Metal binding domains 3 and 4 of the Wilson disease protein: solution structure and interaction with the copper(I) chaperone HAH1. , 2008, Biochemistry.

[209]  T. O’Halloran,et al.  Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[210]  C. Crosio,et al.  Oligomerization of mutant SOD1 in mitochondria of motoneuronal cells drives mitochondrial damage and cell toxicity. , 2009, Antioxidants & redox signaling.

[211]  D. Huffman,et al.  Energetics of Copper Trafficking between the Atx1 Metallochaperone and the Intracellular Copper Transporter, Ccc2* , 2000, The Journal of Biological Chemistry.

[212]  H. Kessler,et al.  The Holo-form of the Nucleotide Binding Domain of the KdpFABC Complex from Escherichia coli Reveals a New Binding Mode* , 2006, Journal of Biological Chemistry.

[213]  D. Thiele,et al.  A widespread transposable element masks expression of a yeast copper transport gene. , 1996, Genes & development.

[214]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.

[215]  I. Bertini,et al.  Solution structure of the Cu(I) and apo forms of the yeast metallochaperone, Atx1. , 2001, Biochemistry.

[216]  P. Nissen,et al.  Dephosphorylation of the Calcium Pump Coupled to Counterion Occlusion , 2004, Science.

[217]  M. Solioz,et al.  Response of Gram-positive bacteria to copper stress , 2009, JBIC Journal of Biological Inorganic Chemistry.

[218]  J. Møller,et al.  Structural organization, ion transport, and energy transduction of P-type ATPases. , 1996, Biochimica et biophysica acta.

[219]  C. Toyoshima,et al.  Interdomain communication in calcium pump as revealed in the crystal structures with transmembrane inhibitors , 2007, Proceedings of the National Academy of Sciences.

[220]  J. Mercer,et al.  The Menkes protein (ATP7A; MNK) cycles via the plasma membrane both in basal and elevated extracellular copper using a C-terminal di-leucine endocytic signal. , 1999, Human molecular genetics.

[221]  S. Lutsenko,et al.  The Copper-transporting ATPases, Menkes and Wilson Disease Proteins, Have Distinct Roles in Adult and Developing Cerebellum* , 2005, Journal of Biological Chemistry.

[222]  H. Kawamata,et al.  Mutant SOD1 in neuronal mitochondria causes toxicity and mitochondrial dynamics abnormalities. , 2009, Human molecular genetics.

[223]  V. Culotta,et al.  The Right to Choose: Multiple Pathways for Activating Copper,Zinc Superoxide Dismutase* , 2009, The Journal of Biological Chemistry.

[224]  I. Bertini,et al.  Mechanism of Cu(A) assembly. , 2008, Nature chemical biology.

[225]  D. Thiele,et al.  Mechanisms for copper acquisition, distribution and regulation. , 2008, Nature chemical biology.

[226]  A. Wernimont,et al.  Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins , 2000, Nature Structural Biology.

[227]  A. K. Mandal,et al.  Functional roles of metal binding domains of the Archaeoglobus fulgidus Cu(+)-ATPase CopA. , 2003, Biochemistry.

[228]  J. Kaplan,et al.  The Mechanism of Copper Uptake Mediated by Human CTR1 , 2005, Journal of Biological Chemistry.

[229]  H. Joh,et al.  A Physiological Role for Saccharomyces cerevisiae Copper/Zinc Superoxide Dismutase in Copper Buffering (*) , 1995, The Journal of Biological Chemistry.