Structural insights into conformational switching in the copper metalloregulator CsoR from Streptomyces lividans.
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.
School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, England.
Tatiana V
TV
Porto
School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, England.
Michael A
MA
Hough
School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, England.
Jonathan A R
JA
Worrall
D001426:Bacterial Proteins / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D048170:Streptomyces lividans / Q000737:chemistry*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D003300:Copper
CsoR; allostery; copper; metalloregulator