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Structural insights into conformational switching in the copper metalloregulator CsoR from<i>Streptomyces lividans</i>

Porto, Tatiana V and Hough, Michael A and Worrall, Jonathan AR (2015) 'Structural insights into conformational switching in the copper metalloregulator CsoR from<i>Streptomyces lividans</i>.' Acta Crystallographica Section D Biological Crystallography, 71 (9). pp. 1872-1878. ISSN 0907-4449

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<jats:p>Copper-sensitive operon repressors (CsoRs) act to sense cuprous ions and bind them with a high affinity under copper stress in many bacteria. The binding of copper(I) leads to a conformational change in their homotetramer structure, causing disassembly of the operator DNA–CsoR complex and evoking a transcriptional response. Atomic-level structural insight into the conformational switching mechanism between the apo and metal-bound states is lacking. Here, a new X-ray crystal structure of the CsoR from<jats:italic>Streptomyces lividans</jats:italic>is reported and compared with a previously reported<jats:italic>S. lividans</jats:italic>CsoR X-ray structure crystallized under different conditions. Based on evidence from this new X-ray structure, it is revealed that the conformational switching between states centres on a concertina effect at the C-terminal end of each α2 helix in the homotetramer. This drives the Cys104 side chain, a copper(I)-ligating residue, into a position enabling copper(I) coordination and as a result disrupts the α2-helix geometry, leading to a compacting and twisting of the homotetramer structure. Strikingly, the conformational switching induces a redistribution of electrostatic surface potential on the tetrameric DNA-binding face, which in the copper(I)-bound state would no longer favour interaction with the mode of operator DNA binding.</jats:p>

Item Type: Article
Uncontrolled Keywords: CsoR; allostery; copper; metalloregulator
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: 04 Sep 2015 10:56
Last Modified: 18 Aug 2022 11:07

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