Mechanistic Aspects of hSOD1 Maturation from the Solution Structure of Cu(I) -Loaded hCCS Domain 1 and Analysis of Disulfide-Free hSOD1 Mutants.
Superoxide dismutase 1 (SOD1) maturation within the cell is mainly accomplished with the SOD1-specific chaperone, CCS, a dimeric protein with three distinct domains in each monomer. We recently showed that the first domain of human CCS (hCCSD1) is responsible for copper transfer to its protein partner, human SOD1 (hSOD1). The NMR solution structure of the copper(I)-loaded form of hCCSD1 reported here contributes further to characterization of the copper-transfer mechanism to hSOD1. NMR spectroscopy was also used to examine the hSOD1 mutants C57A, C146A, and C57A/C146A, which are unable to form the structurally conserved disulfide bond in SOD1, in order to investigate the role of these cysteines during hSOD1 copper acquisition. Together, the information on both hCCS and hSOD1, along with a sequence analysis of eukaryotic CCSD1, allows us to propose important mechanistic aspects regarding the copper-transfer process from hCCS to hSOD1.
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GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-N CHEMICAL GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y
CCS human CCS hCCSD1 SOD1 human SOD1 hSOD1 hCCSD1 hSOD1 hSOD1 C57A Superoxide C146A C57A C146A SOD1 hSOD1 hCCS hSOD1 CCSD1 SOD1-specific chaperone hCCS copper hSOD1 hSOD1 hSOD1 hCCS Domain 1 copper(I) disulfide cysteines copper Disulfide Cu(I) Superoxide dismutase 1