CCS transfers Cu to SOD1 and oxidizes cysteine residues in SOD1

Stable Identifier
Reaction [transition]
Homo sapiens
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Copper chaperone of superoxide dismutase (CCS) transfers a copper(I) atom to a SOD1 monomer that already contains a Zn atom. After initial heterodimerization between SOD1 and CCS, the copper atom is transferred, intramolecular cysteine disulfide bonds are formed in SOD1, and SOD1 dimerizes (Banci et al. 2012, Casareno et al. 1998, Culotta et al. 1997, Rae et al. 2001, Brown et al. 2004, Carroll et al. 2006, Kawamata and Manfredi 2008). The transfer of copper to SOD1 requires oxygen but it is unknown at which step the oxygen acts (Brown et al. 2004). There is also a CCS-independent, oxygen-independent pathway of maturation of SOD1 (Leitch et al. 2009) whose molecular details and physiological role are not well characterized.
Literature References
PubMed ID Title Journal Year
9295278 The copper chaperone for superoxide dismutase

Gitlin, JD, Casareno, RL, Culotta, VC, Krems, B, Strain, J, Klomp, LW

J. Biol. Chem. 1997
9726962 The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase

Gitlin, JD, Casareno, RL, Waggoner, D

J. Biol. Chem. 1998
15064408 Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase

Doan, PE, Brown, NM, O'Halloran, TV, Torres, AS

Proc. Natl. Acad. Sci. U.S.A. 2004
22869735 Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS)

Banci, L, Kozyreva, T, Massagni, C, Zovo, K, Cantini, F, Palumaa, P, Rubino, JT, Bertini, I

Proc. Natl. Acad. Sci. U.S.A. 2012
16880213 The effects of glutaredoxin and copper activation pathways on the disulfide and stability of Cu,Zn superoxide dismutase

Cizewski Culotta, V, Watson, WH, Whitson, LJ, Outten, CE, Carroll, MC, Jensen, LT, Hart, PJ, Rosenfeld, L, Proescher, JB

J. Biol. Chem. 2006
18703498 Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria

Kawamata, H, Manfredi, G

Hum. Mol. Genet. 2008
19542232 Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS

Bouldin, SD, Outten, CE, Jensen, LT, Culotta, VC, Hart, PJ, Leitch, JM

J. Biol. Chem. 2009
11018045 Mechanism of Cu,Zn-superoxide dismutase activation by the human metallochaperone hCCS

O'Halloran, TV, Torres, AS, Rae, TD, Pufahl, RA

J. Biol. Chem. 2001
Catalyst Activity

protein-disulfide reductase activity of CCS:Zn2+:2xCu1+:SOD1:Zn2+ [cytosol]

Orthologous Events
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