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Structural insights into conformational switching in the copper metalloregulator CsoR from Streptomyces lividans

Porto, TV and Hough, MA and Worrall, JAR (2015) 'Structural insights into conformational switching in the copper metalloregulator CsoR from Streptomyces lividans.' Acta Crystallographica Section D: Biological Crystallography, 71. 1872 - 1878. ISSN 0907-4449

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Abstract

© 2015 International Union of Crystallography. 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 Streptomyces lividans is reported and compared with a previously reported S. lividans 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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 04 Sep 2015 10:56
Last Modified: 10 Sep 2019 11:15
URI: http://repository.essex.ac.uk/id/eprint/14771

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