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Structural insights into conformational switching in the copper metalloregulator CsoR from

DOI: 10.1107/S1399004715013012 DOI Help
PMID: 26327377 PMID Help

Authors: T. V. Porto (University of Essex) , M. A. Hough (University of Essex) , J. A. R. Worrall (University of Essex)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 71 , PAGES 1872 - 1878

State: Published (Approved)
Published: September 2015
Diamond Proposal Number(s): 9475

Abstract: 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.

Journal Keywords: Csor; Allostery; Copper; Metalloregulator

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography