Structural basis and mechanism for metallochaperone-assisted assembly of the CuA center in cytochrome oxidase

We demonstrate how two copper atoms are brought together to build a metal center in an essential enzyme for cellular respiration. The mechanisms underlying the biogenesis of the structurally unique, binuclear Cu 1.5+ •Cu 1.5+ redox center (Cu A ) on subunit II (CoxB) of cytochrome oxidases have been...

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Bibliographic Details
Published in:Science advances 2019-07, Vol.5 (7), p.eaaw8478-eaaw8478
Main Authors: Canonica, Fabia, Klose, Daniel, Ledermann, Raphael, Sauer, Maximilian M, Abicht, Helge K, Quade, Nick, Gossert, Alvar D, Chesnov, Serge, Fischer, Hans-Martin, Jeschke, Gunnar, Hennecke, Hauke, Glockshuber, Rudi
Format: Article
Language:English
Subjects:
Biochemistry
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Structural Biology
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Summary:We demonstrate how two copper atoms are brought together to build a metal center in an essential enzyme for cellular respiration. The mechanisms underlying the biogenesis of the structurally unique, binuclear Cu 1.5+ •Cu 1.5+ redox center (Cu A ) on subunit II (CoxB) of cytochrome oxidases have been a long-standing mystery. Here, we reconstituted the CoxB•Cu A center in vitro from apo -CoxB and the holo -forms of the copper transfer chaperones ScoI and PcuC. A previously unknown, highly stable ScoI•Cu 2+ •CoxB complex was shown to be rapidly formed as the first intermediate in the pathway. Moreover, our structural data revealed that PcuC has two copper-binding sites, one each for Cu 1+ and Cu 2+ , and that only PcuC•Cu 1+ •Cu 2+ can release CoxB•Cu 2+ from the ScoI•Cu 2+ •CoxB complex. The CoxB•Cu A center was then formed quantitatively by transfer of Cu 1+ from a second equivalent of PcuC•Cu 1+ •Cu 2+ to CoxB•Cu 2+ . This metalation pathway is consistent with all available in vivo data and identifies the sources of the Cu ions required for Cu A center formation and the order of their delivery to CoxB.
ISSN:2375-2548
DOI:10.1126/sciadv.aaw8478