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Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway in <i>Streptomyces lividans</i>

Blundell, Katie LIM and Hough, Michael A and Vijgenboom, Erik and Worrall, Jonathan AR (2014) 'Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway in <i>Streptomyces lividans</i>.' Biochemical Journal, 459 (3). pp. 525-538. ISSN 0264-6021

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<jats:p>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 co-factoring 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 β-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 copper-binding 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 reaction with Cu(I)–ECuC. Generation of the genetic knockouts, Δsco, Δecuc and Δsco/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.</jats:p>

Item Type: Article
Uncontrolled Keywords: copper chaperone; cytochrome c oxidase; morphological development; Streptomyces
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Sep 2014 11:42
Last Modified: 18 Aug 2022 11:06

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