Copper activation of superoxide dismutase 1 (SOD1) in vivo - Role for protein-protein interactions with the copper chaperone for SOD1

Citation
Pj. Schmidt et al., Copper activation of superoxide dismutase 1 (SOD1) in vivo - Role for protein-protein interactions with the copper chaperone for SOD1, J BIOL CHEM, 275(43), 2000, pp. 33771-33776
Citations number
42
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
43
Year of publication
2000
Pages
33771 - 33776
Database
ISI
SICI code
0021-9258(20001027)275:43<33771:CAOSD1>2.0.ZU;2-Q
Abstract
Insertion of copper into superoxide dismutase 1 (SOD1) in vivo requires the copper chaperone for SOD1 (CCS). CCS encompasses three protein domains: co pper binding Domains I and III at the amino and carboxyl termini, and a cen tral Domain II homologous to SOD1, Using a yeast interaction mating system, yeast CCS was seen to physically interact with SOD1, and this interaction required sequences at the predicted dimer interface of CCS Domain II. Inter actions with SOD1 also required sequences of Domain III, but not Domain I. Mutations were introduced at the dimer interface of yeast SOD1, and the cor responding mutant failed to interact with CCS. When loaded with copper inde pendent of CCS, this mutant SOD1 exhibited superoxide scavenging activity, but was normally inactive in vivo because CCS failed to recognize the enzym e. Activation of SOD1 by CCS was also examined using an in vivo assay for c opper incorporation into SOD1. Yeast CCS was observed to insert copper into a pre-existing pool of apoSOD1 without the need for new SOD1 synthesis or for protein unfolding by the major SSA cytosolic heat shock proteins. Our d ata are consistent with a model in which prefolded dimers of apoSOD1 serve as substrate for the CCS copper chaperone.