Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase

Proceedings of the National Academy of Sciences of the United States of America
Marcos N MorgadaAlejandro J Vila

Abstract

Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion.

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Citations

May 16, 2017·Angewandte Chemie·Arnaud BasléChristopher Dennison
Mar 3, 2018·International Journal of Molecular Sciences·Natanael MansillaElina Welchen
Sep 28, 2017·Metallomics : Integrated Biometal Science·Zakery N BakerScot C Leary
Sep 1, 2018·Protein Science : a Publication of the Protein Society·Liezelle C LopezLaura M Hunsicker-Wang
Jul 28, 2019·The FEBS Journal·María-Eugenia LlasesAlejandro J Vila
Jan 4, 2020·Chemical Communications : Chem Comm·Marcos N MorgadaAlejandro J Vila
Jun 3, 2020·International Journal of Molecular Sciences·Jia Xin TangMonika Oláhová
Aug 8, 2019·International Journal of Molecular Sciences·María-Eugenia LlasesAlejandro J Vila
Sep 27, 2020·International Journal of Molecular Sciences·Shadi MaghoolMegan J Maher
Sep 6, 2017·Seminars in Cell & Developmental Biology·Alba Timón-GómezAntoni Barrientos
Sep 27, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Paul A CobineScot C Leary
Feb 9, 2021·Genome Génome / Conseil National De Recherches Canada·Fátima Yedith Camacho-SánchezMiguel Angel Reyes-López
Aug 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·May T MaungTeresita Padilla-Benavides
Jun 30, 2018·Inorganic Chemistry·Biplab K MaitiJosé J G Moura
Jan 16, 2019·Inorganic Chemistry·Ulises A ZitareDaniel H Murgida
Sep 11, 2021·Frontiers in Molecular Biosciences·Lina M RuizAlvaro A Elorza

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