Title of article :
Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis
Author/Authors :
Shohei Watanabe، نويسنده , , Seiichi Nagano، نويسنده , , James Duce، نويسنده , , Mahmoud Kiaei، نويسنده , , Qiao-Xin Li، نويسنده , , Stephanie M. Tucker، نويسنده , , Ashutosh Tiwari، نويسنده , , Robert H. Brown Jr.، نويسنده , , M. Flint Beal، نويسنده , , Lawrence J. Hayward، نويسنده , , Valeria C. Culotta، نويسنده , , Satoshi Yoshihara، نويسنده , , Saburo Sakoda، نويسنده , , Ashley I. Bush، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
Pages :
9
From page :
1534
To page :
1542
Abstract :
Mutations in Cu,Zn-superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (ALS). It has been proposed that neuronal cell death might occur due to inappropriately increased Cu interaction with mutant SOD1. Using Cu immobilized metal-affinity chromatography (IMAC), we showed that mutant SOD1 (A4V, G85R, and G93A) expressed in transfected COS7 cells, transgenic mouse spinal cord tissue, and transformed yeast possessed higher affinity for Cu than wild-type SOD1. Serine substitution for cysteine at the Cys111 residue in mutant SOD1 abolished the Cu interaction on IMAC. C111S substitution reversed the accelerated degradation of mutant SOD1 in transfected cells, suggesting that the Cys111 residue is critical for the stability of mutant SOD1. Aberrant Cu binding at the Cys111 residue may be a significant factor in altering mutant SOD1 behavior and may explain the benefit of controlling Cu access to mutant SOD1 in models of familial ALS.
Keywords :
Amyotrophic lateral sclerosis , Cu , Zn-superoxide dismutase , copper , Immobilized metal affinity chromatography , Cu chaperone for SOD1 , Cysteine , protein stability , oxidative stress , free radicals
Journal title :
Free Radical Biology and Medicine
Serial Year :
2007
Journal title :
Free Radical Biology and Medicine
Record number :
520950
Link To Document :
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