scholarly journals Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis

2012 ◽  
Vol 22 (1) ◽  
pp. 51-60 ◽  
Author(s):  
K. S. Graffmo ◽  
K. Forsberg ◽  
J. Bergh ◽  
A. Birve ◽  
P. Zetterstrom ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Superoxide Dismutase 1 ◽  
Wild Type ◽  
Lateral Sclerosis

scholarly journals Mutations in Superoxide Dismutase 1 (Sod1) Linked to Familial Amyotrophic Lateral Sclerosis Can Disrupt High-Affinity Zinc-Binding Promoted by the Copper Chaperone for Sod1 (Ccs)

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1086 ◽  
Author(s):  
Stefanie D. Boyd ◽  
Morgan S. Ullrich ◽  
Jenifer S. Calvo ◽  
Fatemeh Behnia ◽  
Gabriele Meloni ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Zinc Binding ◽  
Copper Chaperone ◽  
Superoxide Dismutase 1 ◽  
Wild Type ◽  
High Affinity ◽  
Familial Form ◽  
First Time ◽  
Lateral Sclerosis

Zinc (II) ions (hereafter simplified as zinc) are important for the structural and functional activity of many proteins. For Cu, Zn superoxide dismutase (Sod1), zinc stabilizes the native structure of each Sod1 monomer, promotes homo-dimerization and plays an important role in activity by “softening” the active site so that copper cycling between Cu(I) and Cu(II) can rapidly occur. Previously, we have reported that binding of Sod1 by its copper chaperone (Ccs) stabilizes a conformation of Sod1 that promotes site-specific high-affinity zinc binding. While there are a multitude of Sod1 mutations linked to the familial form of amyotrophic lateral sclerosis (fALS), characterizations by multiple research groups have been unable to realize strong commonalities among mutants. Here, we examine a set of fALS-linked Sod1 mutations that have been well-characterized and are known to possess variation in their biophysical characteristics. The zinc affinities of these mutants are evaluated here for the first time and then compared with the previously established value for wild-type Sod1 zinc affinity. Ccs does not have the same ability to promote zinc binding to these mutants as it does for the wild-type version of Sod1. Our data provides a deeper look into how (non)productive Sod1 maturation by Ccs may link a diverse set of fALS-Sod1 mutations.

scholarly journals Glial nuclear aggregates of superoxide dismutase-1 are regularly present in patients with amyotrophic lateral sclerosis

2011 ◽  
Vol 121 (5) ◽  
pp. 623-634 ◽  
Author(s):  
Karin Forsberg ◽  
Peter M. Andersen ◽  
Stefan L. Marklund ◽  
Thomas Brännström
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Superoxide Dismutase 1 ◽  
Lateral Sclerosis
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