The high concentration of Arg213-->Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities.
The C-terminal region of EC-SOD (extracellular superoxide dismutase) mediates the binding to both heparin/heparan sulphate and type I collagen. A mutation (Arg213-->Gly; R213G) within this extracellular matrix-binding region has recently been implicated in the development of heart disease. This relatively common mutation affects the heparin affinity, and the concentration of EC-SOD in the plasma of R213G homozygous individuals is increased 10- to 30-fold. In the present study we confirm, using R213G EC-SOD purified from a homozygous individual, that the heparin affinity is reduced. Significantly, the collagen affinity of the R213G EC-SOD variant was similarly affected and both the heparin and collagen affinities were reduced by 12-fold. Structural analysis of synthetic extracellular matrix-binding regions suggests that the mutation alters the secondary structure. We conclude that the increased concentration of EC-SOD in the plasma of R213G carriers is caused by a reduction in both heparin and collagen affinities.
Petersen
Steen V
SV
Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
Olsen
Dorte Aa
DA
Kenney
John M
JM
Oury
Tim D
TD
Valnickova
Zuzana
Z
Thøgersen
Ida B
IB
Crapo
James D
JD
Enghild
Jan J
JJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001011:Aorta / Q000201:enzymology; D001120:Arginine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002846:Chromatography, Affinity / Q000379:methods; D002847:Chromatography, Agarose / Q000379:methods; D002942:Circular Dichroism / Q000379:methods; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D010455:Peptides; D006493:Heparin; D003094:Collagen; D001120:Arginine; C441642:SOD3 protein, human; D013482:Superoxide Dismutase; D005998:Glycine