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. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form / L.Banci; I.Bertini; F.Cantini; N.D'Amelio; E.Gaggelli. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 281:(2006), pp. 2333-2337. [10.1074/jbc.M506497200]

Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form

BANCI, LUCIA;BERTINI, IVANO;CANTINI, FRANCESCA;
2006

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. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
2006
281
2333
2337
L.Banci; I.Bertini; F.Cantini; N.D'Amelio; E.Gaggelli
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/203005
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