One gene, two proteins: coordinated production of a copper chaperone by differential transcript formation and translational frameshifting in Escherichia coli

Mol Microbiol. 2017 Nov;106(4):635-645. doi: 10.1111/mmi.13841. Epub 2017 Oct 6.


Programmed ribosomal frameshifting (PRF) is a translational anomaly causing the ribosome to shift into an alternative reading frame. PRFs are common in viral genomes, using a single nucleotide sequence to code for two proteins in overlapping frames. In bacteria and eukaryota, PRFs are less frequent. We report on a PRF in the copper detoxification system of Escherichia coli where a metallochaperone is generated out of the first 69 amino acids and a C-terminal out-of-frame glycine of the gene copA. copA besides codes for the P1B -ATPase CopA, a membrane-integral protein and principal interaction target of the chaperone. To enhance the production of the frameshift-generated cytosolic copper binding protein a truncated transcript is produced from the monocistronic copA gene. This shorter transcript is essential for producing sufficient amounts of the chaperone to support the membrane pump. The findings close the gap in our understanding of the molecular physiology of cytoplasmic copper transport in E. coli, revealing that a chaperone-like entity is required for full functionality of the P1B -ATPase copper pump. We, moreover, demonstrate that the primary transcriptional response to copper results in formation of the small transcript and concurrently, the metallochaperone plays a key role in resistance against copper shock.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Biological Transport
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Copper / metabolism
  • Copper-Transporting ATPases / genetics*
  • Copper-Transporting ATPases / metabolism*
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism*
  • Frameshifting, Ribosomal / genetics
  • Gene Expression Regulation, Bacterial / genetics
  • Membrane Proteins / metabolism
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Mutation
  • Ribosomes / metabolism


  • Bacterial Proteins
  • Carrier Proteins
  • Cation Transport Proteins
  • Escherichia coli Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • copper-binding protein
  • Copper
  • Adenosine Triphosphatases
  • Copper-Transporting ATPases
  • copA protein, E coli