Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13555-60. doi: 10.1073/pnas.1207493109. Epub 2012 Aug 6.

Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS).

Author information

1
Magnetic Resonance Center, University of Florence, 50019 Sesto Fiorentino, Italy. banci@cerm.unifi.it

Abstract

Copper chaperone for superoxide dismutase 1 (SOD1), CCS, is the physiological partner for the complex mechanism of SOD1 maturation. We report an in vitro model for human CCS-dependent SOD1 maturation based on the study of the interactions of human SOD1 (hSOD1) with full-length WT human CCS (hCCS), as well as with hCCS mutants and various truncated constructs comprising one or two of the protein's three domains. The synergy between electrospray ionization mass spectrometry (ESI-MS) and NMR is fully exploited. This is an in vitro study of this process at the molecular level. Domain 1 of hCCS is necessary to load hSOD1 with Cu(I), requiring the heterodimeric complex formation with hSOD1 fostered by the interaction with domain 2. Domain 3 is responsible for the catalytic formation of the hSOD1 Cys-57-Cys-146 disulfide bond, which involves both hCCS Cys-244 and Cys-246 via disulfide transfer.

PMID:
22869735
PMCID:
PMC3427097
DOI:
10.1073/pnas.1207493109
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center