An atypical linear Cu(I)-S2 center constitutes the high-affinity metal-sensing site in the CueR metalloregulatory protein

Kui Chen, Saodat Yuldasheva, James E. Penner-Hahn, Thomas V. O'Halloran*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

CueR is a copper-responsive genetic switch that regulates transcription of genes encoding the primary copper-exporting system in E. coli, CopA and CueO. Although a member of the MerR family of regulatory proteins, CueR has four cysteines in an array that is distinct from those in Hg(II)-sensing MerR or in Zn-sensing ZntR. A recent crystal structure showed one copper atom in CueR bound to cysteines Cys112 and Cys120 in a linear CuS2 structure, but left open the questions of whether the other half of the CueR dimer has the same structure, and of whether these structures depend on the two additional C-terminal cysteines. Metal binding, transcription runoff, and cysteine modification studies show that only Cys112 and Cys 120 are necessary and sufficient to make the transcriptionally active Cu-sensing site. X-ray absorption spectroscopy shows that this site binds Cu(I) in a strictly linear CuS2 site in solution, a structure that is rarely observed in copper proteins. This structure does not depend either on additional metal loading or upon the presence of additional C-terminal cysteine ligands and is well suited for an ultrasensitve receptor site that discriminates against the binding of other metal ions.

Original languageEnglish (US)
Pages (from-to)12088-12089
Number of pages2
JournalJournal of the American Chemical Society
Volume125
Issue number40
DOIs
StatePublished - Oct 8 2003

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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