Abstract
Cu+-ATPases play a key role in bacterial Cu+ homeostasis by participating in Cu+ detoxification and cuproprotein assembly. Characterization of Archaeoglobus fulgidus CopA, a model protein within the subfamily of P1B-1 type ATPases, has provided structural and mechanistic details on this group of transporters. Atomic resolution structures of cytoplasmic regulatory metal binding domains (MBDs) and catalytic actuator, phosphorylation, and nucleotide binding domains are available. These, in combination with whole protein structures resulting from cryo-electron microscopy analyses, have enabled the initial modeling of these transporters. Invariant residues in helixes 6, 7 and 8 form two transmembrane metal binding sites (TM-MBSs). These bind Cu+ with high affinity in a trigonal planar geometry. The cytoplasmic Cu+ chaperone CopZ transfers the metal directly to the TM-MBSs; however, loading both of the TM-MBSs requires binding of nucleotides to the enzyme. In agreement with the classical transport mechanism of P-type ATPases, occupancy of both transmembrane sites by cytoplasmic Cu+ is a requirement for enzyme phosphorylation and subsequent transport into the periplasmic or extracellular milieus. Recent transport studies have shown that all Cu+-ATPases drive cytoplasmic Cu+ efflux, albeit with quite different transport rates in tune with their various physiological roles. Archetypical Cu+-efflux pumps responsible for Cu+ tolerance, like the Escherichia coli CopA, have turnover rates ten times higher than those involved in cuproprotein assembly (or alternative functions). This explains the incapability of the latter group to significantly contribute to the metal efflux required for survival in high copper environments.
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Notes
For simplicity P-type ATPases will be referred as P-ATPases, P1B-ATPases, etc.
References
Agranoff D, Krishna S (2004) Metal ion transport and regulation in Mycobacterium tuberculosis. Front Biosci 9:2996–3006
Argüello JM (2003) Identification of ion-selectivity determinants in heavy-metal transport P1B-type ATPases. J Membr Biol 195:93–108
Argüello JM, Eren E, González-Guerrero M (2007) The structure and function of heavy metal transport P1B-ATPases. Biometals 20:233–248
Axelsen KB, Palmgren MG (1998) Evolution of substrate specificities in the P-type ATPase superfamily. J Mol Evol 46:84–101
Bagai I, Rensing C, Blackburn NJ, McEvoy MM (2008) Direct metal transfer between periplasmic proteins identifies a bacterial copper chaperone. Biochemistry 47:11408–11414
Boal AK, Rosenzweig AC (2009) Structural biology of copper trafficking. Chem Rev 109:4760–4779
Brunori M, Giuffre A, Sarti P (2005) Cytochrome c oxidase, ligands and electrons. J Inorg Biochem 99:324–336
Chintalapati S, Al Kurdi R, van Scheltinga ACT, Kuehlbrandt W (2008) Membrane structure of CtrA3, a copper-transporting P-type-ATPase from Aquifex aeolicus. J Mol Biol 378:581–595
Desideri A, Falconi M (2003) Prokaryotic Cu, Zn superoxidies dismutases. Biochem Soc Trans 31:1322–1325
Eisses JF, Kaplan JH (2002) Molecular characterization of hCTR1, the human copper uptake protein. J Biol Chem 277:29162–29171
Espariz M, Checa SK, Audero ME, Pontel LB, Soncini FC (2007) Dissecting the Salmonella response to copper. Microbiology 153:2989–2997
Fan B, Rosen BP (2002) Biochemical characterization of CopA, the Escherichia coli Cu(I)-translocating P-type ATPase. J Biol Chem 277:46987–46992
Francis MS, Thomas CJ (1997) The Listeria monocytogenes gene ctpA encodes a putative P-type ATPase involved in copper transport. Mol Gen Genet 253:484–491
Frangipani E, Haas D (2009) Copper acquisition by the SenC protein regulates aerobic respiration in Pseudomonas aeruginosa PAO1. FEMS Microbiol Lett 298:234–240
Fraústro da Silva JJR, Williams RJP (2001) The biological chemistry of the elements. Oxford University Press, New York
González-Guerrero M, Argüello JM (2008) Mechanism of Cu+-transporting ATPases: Soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites. Proc Nat Acad Sci USA 105:5992–5997
González-Guerrero M, Eren E, Rawat S, Stemmler TL, Argüello JM (2008) Structure of the two transmembrane Cu+ transport sites of the Cu+-ATPases. J Biol Chem 283:29753–29759
González-Guerrero M, Hong D, Argüello JM (2009) Chaperone-mediated Cu+ delivery to Cu+ transport ATPases. Requirement of nucleotide binding. J Biol Chem 284:20804–20811
González-Guerrero M, Raimunda D, Cheng X, Argüello JM (2010) Distinct functional roles of homologous Cu+ efflux ATPases in Pseudomonas aeruginosa. Mol Microbiol 78:1246–1258
Hassani BK, Astier C, Nitschke W, Ouchane S (2010) CtpA, a copper-translocating P-type ATPase involved in the biogenesis of multiple copper-requiring enzymes. J Biol Chem 285:19330–19337
Hatori Y, Majima E, Tsuda T, Toyoshima C (2007) Domain organization and movements in heavy metal ion pumps: papain digestion of CopA, a Cu+-transporting ATPase. J Biol Chem 282:25213–25221
Hatori Y, Hirata A, Toyoshima C, Lewis D, Pilankatta R, Inesi G (2008) Intermediate phosphorylation reactions in the mechanism of ATP utilization by the copper ATPase (CopA) of Thermotoga maritima. J Biol Chem 283:22541–22549
Huffman DL, Huyett J, Outten FW, Doan PE, Finney LA, Hoffman BM, O’Halloran TV (2002) Spectroscopy of Cu(II)-PcoC and the multicopper oxidase function of PcoA, two essential components of Escherichia coli pco copper resistance operon. Biochemistry 41:10046–10055
Jabs T, Tschope M, Colling C, Hahlbrock K, Scheel D (1997) Elicitor-stimulated ion fluxes and O2(−) from the oxidative burst are essential components in triggering defense gene activation and phytoalexin synthesis in parsley. Proc Nat Acad Sci USA 94:4800–4805
Kanamaru K, Kashiwagi S, Mizuno T (1994) A copper-transporting P-type ATPase found in the thylakoid membrane of the cyanobacterium Synechococcus species PCC7942. Mol Microbiol 13:369–377
Koch HG, Winterstein C, Saribas AS, Alben JO, Daldal F (2000) Roles of the ccoGHIS gene products in the biogenesis of the cbb 3-type cytochrome c oxidase. J Mol Biol 297:49–65
Levine A, Tenhaken R, Dixon R, Lamb C (1994) H2O2 from the oxidative burst orchestrates the plant hypersensitive disease resistance response. Cell 79:583–593
Long F, Su CC, Zimmermann MT, Boyken SE, Rajashankar KR, Jernigan RL, Yu EW (2010) Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport. Nature 467:484–488
Lubben M, Guldenhaupt J, Zoltner M, Deigweiher K, Haebel P, Urbanke C, Scheidig AJ (2007) Sulfate acts as phosphate analog on the monomeric catalytic fragment of the CPx-ATPase CopB from Sulfolobus solfataricus. J Mol Biol 369:368–385
Ma Z, Jacobsen FE, Giedroc DP (2009) Coordination chemistry of bacterial metal transport and sensing. Chem Rev 109:4644–4681
Macomber L, Imlay JA (2009) The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc Natl Acad Sci USA 106:8344–8349
Mandal AK, Argüello JM (2003) Functional roles of metal binding domains of the Archaeoglobus fulgidus Cu+-ATPase CopA. Biochemistry 42:11040–11047
Mandal AK, Cheung WD, Argüello JM (2002) Characterization of a thermophilic P-type Ag+/Cu+-ATPase from the extremophile Archaeoglobus fulgidus. J Biol Chem 277:7201–7208
Mandal AK, Yang Y, Kertesz TM, Argüello JM (2004) Identification of the transmembrane metal binding site in Cu+-transporting PIB-type ATPases. J Biol Chem 279:54802–54807
Morth JP, Pedersen BP, Toustrup-Jensen MS, Sorensen TL, Petersen J, Andersen JP, Vilsen B, Nissen P (2007) Crystal structure of the sodium-potassium pump. Nature 450:1043–1049
O’Halloran TV, Culotta VC (2000) Metallochaperones, an intracellular shuttle service for metal ions. J Biol Chem 275:25057–25060
Odermatt A, Suter H, Krapf R, Solioz M (1993) Primary structure of two P-type ATPases involved in copper homeostasis in Enterococcus hirae. J Biol Chem 268:12775–12779
Olesen C, Picard M, Winther AM, Gyrup C, Morth JP, Oxvig C, Moller JV, Nissen P (2007) The structural basis of calcium transport by the calcium pump. Nature 450:1036–1042
Osman D, Cavet JS (2008) Copper homeostasis in bacteria. Adv Appl Microbiol 65:217–247
Pedersen BP, Buch-Pedersen MJ, Morth JP, Palmgren MG, Nissen P (2007) Crystal structure of the plasma membrane proton pump. Nature 450:1111–1114
Petit-Haertlein I, Girard E, Sarret G, Hazemann JL, Gourhant P, Kahn R, Coves J (2010) Evidence for conformational changes upon copper binding to Cupriavidus metallidurans CzcE. Biochemistry 49:1913–1922
Phung LT, Ajlani G, Haselkorn R (1994) P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products. Proc Natl Acad Sci U S A 91:9651–9654
Pontel LB, Audero MEP, Espariz M, Checa SK, Soncini FC (2007) GoIS controls the response to gold by the hierarchical induction of Salmonella-specific genes that include a CBA efflux-coding operon. Mol Microbiol 66:814–825
Preisig O, Zufferey R, Hennecke H (1996) The Bradyrhizobium japonicum fixGHIS genes are required for the formation of the high-affinity cbb 3-type cytochrome oxidase. Arch Microbiol 165:297–305
Puig S, Lee J, Lau M, Thiele DJ (2002) Biochemical and genetic analyses of yeast and human high affinity copper transporters suggest a conserved mechanism for copper uptake. J Biol Chem 277:26021–26030
Rensing C, Fan B, Sharma R, Mitra B, Rosen BP (2000) CopA: an Escherichia coli Cu(I)-translocating P-type ATPase. Proc Natl Acad Sci USA 97:652–656
Robinson NJ (2008) A bacterial copper metallothionein. Nature Chem Biol 4:582–583
Robinson NJ, Winge DR (2010) Copper metallochaperones. Annu Rev Biochem 79:537–562
Saier MH Jr (2006) Protein secretion and membrane insertion systems in gram-negative bacteria. J Membr Biol 214:75–90
Sazinsky MH, Agarwal S, Arguello JM, Rosenzweig AC (2006a) Structure of the actuator domain from the Archaeoglobus fulgidus Cu+-ATPase. Biochemistry 45:9949–9955
Sazinsky MH, Mandal AK, Arguello JM, Rosenzweig AC (2006b) Structure of the ATP binding domain from the Archaeoglobus fulgidus Cu+-ATPase. J Biol Chem 281:11161–11166
Sazinsky MH, LeMoine B, Orofino M, Davydov R, Bencze KZ, Stemmler TL, Hoffman BM, Arguello JM, Rosenzweig AC (2007) Characterization and structure of a Zn2+ and [2Fe-2S]-containing copper chaperone from Archaeoglobus fulgidus. J Biol Chem 282:25950–25959
Schwan WR, Warrener P, Keunz E, Stover CK, Folger KR (2005) Mutations in the cueA gene encoding a copper homeostasis P-type ATPase reduce the pathogenicity of Pseudomonas aeruginosa in mice. Int J Med Microbiol 295:237–242
Solioz M, Abicht HK, Mermod M, Mancini S (2010) Response of gram-positive bacteria to copper stress. J Biol Inorg Chem 15:3–14
Su CC, Yang F, Long F, Reyon D, Routh MD, Kuo DW, Mokhtari AK, Van Ornam JD, Rabe KL, Hoy JA, Lee YJ, Rajashankar KR, Yu EW (2009) Crystal structure of the membrane fusion protein CusB from Escherichia coli. J Mol Biol 393:342–355
Tottey S, Rich PR, Rondet SAM, Robinson NJ (2001) Two Menkes-type ATPases supply copper for photosynthesis in Synechocystis PCC 6803. J Biol Chem 276:19999–20004
Tottey S, Harvie DR, Robinson NJ (2005) Understanding how cells allocate metals using metal sensors and metallochaperones. Acc Chem Res 38:775–783
Toyoshima C (2008) Structural aspects of ion pumping by Ca2+-ATPase of sarcoplasmic reticulum. Arch Biochem Biophys 476:3–11
Tsivkovskii R, MacArthurs B, Lutsenko S (2001) The Lys(1010)-Lys(1325) fragment of the Wilson’s disease protein binds nucleotides and interacts with the N-terminal domain of this protein in a copper-dependent manner. J Biol Chem 276:2234–2242
Tsuda T, Toyoshima C (2009) Nucleotide recognition by CopA, a Cu+-transporting P-type ATPase. EMBO J 28:1782–1791
White C, Lee J, Kambe T, Fritsche K, Petris MJ (2009) A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem 284:33949–33956
Wu CC, Rice WJ, Stokes DL (2008) Structure of a copper pump suggests a regulatory role for its metal-binding domain. Structure 16:976–985
Zhang XX, Rainey PB (2007) The role of a P1-type ATPase from Pseudomonas fluorescens SBW25 in copper homeostasis and plant colonization. Mol Plant Microbe Interact 20:581–588
Acknowledgments
This work was supported by grants National Institute of Health 1R21AI082484-01, National Institute of Food and Agriculture 2010-65108-20606 and National Science Foundation MCB-0743901. We thank Dr. Robert L. Burnap, Oklahoma State University, for helpful discussions and providing us with Synechocystis PCC 6803.
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Raimunda, D., González-Guerrero, M., Leeber, B.W. et al. The transport mechanism of bacterial Cu+-ATPases: distinct efflux rates adapted to different function. Biometals 24, 467–475 (2011). https://doi.org/10.1007/s10534-010-9404-3
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DOI: https://doi.org/10.1007/s10534-010-9404-3