Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form.
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Banci L, Bertini I, Cantini F, D'Amelio N, Gaggelli E
Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form.
J Biol Chem. 2006 Jan 27;281(4):2333-7. Epub 2005 Nov 14.
- PubMed ID
- 16291742 [ View in PubMed]
- Abstract
SOD1 has to undergo several post-translational modifications before reaching its mature form. The protein requires insertion of zinc and copper atoms, followed by the formation of a conserved S-S bond between Cys-57 and Cys-146 (human numbering), which makes the protein fully active. In this report an NMR structural investigation of the reduced SH-SH form of thermostable E,Zn-as-SOD1 (E is empty; as is C6A, C111S) is reported, characterizing the protein just before the last step leading to the mature form. The structure is compared with that of the oxidized S-S form as well as with that of the yeast SOD1 complexed with its copper chaperone, CCS. Local conformational rearrangements upon disulfide bridge reduction are localized in the region near Cys-57 that is completely exposed to the solvent in the present structure, at variance with the oxidized forms. There is a local disorder around Cys-57 that may serve for protein-protein recognition and may possibly be involved in intermolecular S-S bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The structure allows us to further discuss the copper loading mechanism in SOD1.