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The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase
R L Casareno1, D Waggoner, J D Gitlin
1Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Journal of Biological Chemistry
|September 3, 1998
Summary
Mutations in copper/zinc superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (FALS). The copper chaperone for SOD1 (CCS) interacts with SOD1, suggesting a therapeutic target for FALS.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Familial amyotrophic lateral sclerosis (FALS) is a fatal motor neuron disease.
- Dominantly inherited mutations in copper/zinc superoxide dismutase (SOD1) are a known cause of FALS.
- Mutant SOD1 gains function, leading to neuronal degeneration via free radical damage.
Purpose of the Study:
- To investigate the interaction between SOD1 and its copper chaperone, CCS.
- To determine if CCS interacts with both wild-type and mutant SOD1.
- To explore the potential of this interaction as a therapeutic target for FALS.
Main Methods:
- Amino acid sequence alignment of SOD1 and CCS.
- In vitro and in vivo interaction studies between SOD1 and CCS.
- Analysis of CCS interaction with wild-type and FALS-associated SOD1 mutants.
Main Results:
- SOD1 and CCS share homologous domains essential for homodimerization.
- CCS directly interacts with both wild-type SOD1 and various FALS-associated SOD1 mutants.
- The interaction between CCS and SOD1 occurs both in vitro and in vivo.
Conclusions:
- CCS and SOD1 interact through homologous domains.
- This interaction involves both normal and mutant SOD1, including FALS-associated forms.
- Targeting the CCS-SOD1 interaction may offer a novel therapeutic strategy for FALS patients.