Copper chaperone for superoxide dismutase

The sequence for delivery of copper ions to SOD1 passes from the copper transporter (Ctr) by an unknown pathway to the copper chaperone for SOD1 (CCS) and by a studied pathway from CCS to SOD1. The CCS protein has been studied structurally and found to be similar to other copper chaperones such as those discussed above—Atxl and Atoxl (Hahl). Copper chaperone for superoxide dismutase (CCS) differs from other copper metallochaperones in that it folds into three functionally distinct protein domains with the N-terminal end of domain I... 

CCS = copper chaperone for superoxide dismutase Moco = molybdenum cofactor MPT = molybdopterin FeMoco = iron-molybdenum cofactor of nitrogenase, SODl = Cu/Zn superoxide dismutase. 

ACS = anunonium (-l-)-DlO-camphorsulfonate BSA = bovine serum albumin CD = circular dichroism CT = charge transfer hCCS = human copper chaperone for superoxide dismutase hSCAN = human soluble calcium-activated nucleotidase-1 LMCT = ligand-to-metal charge transfer METP = miniaturized electron transfer protein MECT = metal-ligand charge transfer ORD = optical rotatory dispersion SODs = superoxide dismutases tCCS = tomato copper chaperone for superoxide dismutase UTP = uracil triphosphate. 

Rae TD, Schmidt PJ, Pufahl RA, Culotta VC, O Halloran TV. Undetectable intracellular free copper the requirement of a copper chaperone for superoxide dismutase. Science 1999 284 805-808. Cobine PA, Ojeda LD, Rigby KM, Winge DR. Yeast contain a non-proteinaceous pool of copper in the mitochondrial matrix. J. Biol. Chem. 2004 279 14447-14455. 

Rae, T.D. 1999. Undetectable Intracellular Free Copper The Requirement of a Copper Chaperone for Superoxide Dismutase. Science, 284(5415), 805-808. 

III. Copper Chaperones for Copper-Zinc Superoxide Dismutase. 180... 

CCS copper chaperone for the largely cytosolic Cu/Zn superoxide dismutase... 

From One Type 2 Copper Protein to Another Type 2 Copper Protein. It has been shown that a type 2 copper protein called copper-zinc superoxide dismutase (CuZnSOD) (Figure 15b) shares the same overall scaffold as its copper chaperone protein called copper chaperone for SOD (CCS). All of e zinc site ligands and three of four copper site histidine ligands in CuZnSOD are conserved in human CCS (hCCS). The zinc site in hCCS displayed the same structure as in CuZnSOD. The fourth ligand in the copper site of CuZnSOD is replaced by an aspartate residue in hCCS. Although aspartate could... 

Figure 1 Copper trafficking pathways in yeast. Atx, antioxidant Ccci, cross-compiements Ca -sensitive phenotype of csgl CCS, copper chaperone for SOD COX, cytochrome c oxidase Ctr, copper transporter Fet, ferrous transport Fre, FerriReductase-encoding Ftr, Fe transporter IMS, intermembrane space MT, metaiiothienoin Sco, suppressor of cytochrome c oxidase deficiency SOD, superoxide dismutase. Reproduced from F. Arnesano L. Banci, In Handbook of Metalloproteins, A. Messerschmidt, Ed. John Wiley Sons Chichester, 2007 Voi. 4, pp 1-21, with permission from John Wiiey Sons.

Figure 12.2 Copper chaperone function, (a) Copper homeostasis in Enterococcus hirae is affected by the proteins encoded by the cop operon. CopA, Cu1+-import ATPase CopB, Cu1+-export ATPase CopY, Cu1+-responsive repressor copZ, chaperone for Cu1+ delivery to CopY. (b) The CTR family of proteins transports copper into yeast cells. Atxlp delivers copper to the CPx-type ATPases located in the post Golgi apparatus for the maturation of Fet3p. (c) Coxl7p delivers copper to the mitochondrial intermembrane space for incorporation into cytochrome c oxidase (CCO). (d) hCTR, a human homologue of CTR, mediates copper-ion uptake into human cells. CCS delivers copper to cytoplasmic Cu/Zn superoxide dismutase (SOD1). Abbreviations IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane PM, plasma membrane PGV, post Golgi vessel. Reprinted from Harrison et al., 2000. Copyright (2000), with permission from Elsevier Science.

As we will discuss later, in Chapter 8, free copper levels are extremely low within cells because the copper is bound to a family of metallochaperones, which are subsequently involved in the incorporation of copper into copper-containing proteins. The mechanism proposed for copper insertion into the Cu/Zn superoxide dismutase, SOD1, is presented in Figure 3.9. The copper chaperone, CCS, acquires copper as Cu+ from a copper transporter and then docks with the reduced dithiol form of SOD1 (Steps I and II) to give a docked... 

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