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Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway in Streptomyces lividans

Blundell, KLIM and Hough, MA and Vijgenboom, E and Worrall, JAR (2014) 'Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway in Streptomyces lividans.' Biochemical Journal, 459 (3). 525 - 538. ISSN 0264-6021

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In Streptomyces lividans an extracytoplasmic copper-binding Sco protein plays a role in two unlinked processes: (i) initiating a morphological development switch and (ii) facilitating the cofactoring of the CuA domain of CcO (cytochrome c oxidase). How Sco obtains copper once secreted to the extracytoplasmic environment is unknown. In the present paper we report on a protein possessing an HX6MX21HXM motif that binds a single cuprous ion with subfemtomolar affinity. High-resolution X-ray structures of this extracytoplasmic copper chaperone-like protein (ECuC) in the apo-and Cu(I)-bound states reveal that the latter possesses a surface-accessible cuprous-ion-binding site located in a dish-shaped region of ß-sheet structure. A cuprous ion is transferred under a favourable thermodynamic gradient from ECuC to Sco with no back transfer occurring. The ionization properties of the cysteine residues in the Cys86xxxCys90 copperbinding motif of Sco, together with their positional locations identified from an X-ray structure of Sco, suggests a role for Cys86 in initiating an inter-complex ligand-exchange reactionwith Cu(I)-ECuC. Generation of the genetic knockouts, ?sco, ?ecuc and ?sco/ecuc, and subsequent in vivo assays lend support to the existence of a branched extracytoplasmic copper-trafficking pathway in S. lividans. One branch requires both Sco and to a certain extent ECuC to cofactor the CuA domain, whereas the other uses only Sco to deliver copper to a cuproenzyme to initiate morphological development. © The Authors Journal compilation © 2014 Biochemical Society.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Mike Hough
Date Deposited: 11 Sep 2014 11:42
Last Modified: 19 Aug 2019 17:15

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