Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH

Mol Cell. 2003 Mar;11(3):659-69. doi: 10.1016/s1097-2765(03)00068-6.


FtsH, a member of the AAA family of proteins, is the only membrane ATP-dependent protease universally conserved in prokaryotes, and the only essential ATP-dependent protease in Escherichia coli. We investigated the mechanism of degradation by FtsH. Other well-studied ATP-dependent proteases use ATP to unfold their substrates. In contrast, both in vitro and in vivo studies indicate that degradation by FtsH occurs efficiently only when the substrate is a protein of low intrinsic thermodynamic stability. Because FtsH lacks robust unfoldase activity, it is able to use the protein folding state of substrates as a criterion for degradation. This feature may be key to its role in the cell and account for its ubiquitous distribution among prokaryotic organisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Dependent Proteases
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Escherichia coli / metabolism
  • Escherichia coli Proteins
  • Green Fluorescent Proteins
  • Heat-Shock Proteins / metabolism
  • Kinetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Plasmids / metabolism
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • RNA, Bacterial / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleases / metabolism
  • Sigma Factor*
  • Substrate Specificity
  • Temperature
  • Thermodynamics
  • Time Factors
  • Transcription Factors / metabolism


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Heat-Shock Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • RNA, Bacterial
  • Recombinant Fusion Proteins
  • Sigma Factor
  • Transcription Factors
  • heat-shock sigma factor 32
  • tmRNA
  • Green Fluorescent Proteins
  • Adenosine Triphosphate
  • Ribonucleases
  • Bacillus amyloliquefaciens ribonuclease
  • ATP-Dependent Proteases
  • FtsH protein, E coli
  • Adenosine Triphosphatases