ATP-dependent proteases differ substantially in their ability to unfold globular proteins

J Biol Chem. 2009 Jul 10;284(28):18674-84. doi: 10.1074/jbc.M900783200. Epub 2009 Apr 21.


ATP-dependent proteases control the concentrations of hundreds of regulatory proteins and remove damaged or misfolded proteins from cells. They select their substrates primarily by recognizing sequence motifs or covalent modifications. Once a substrate is bound to the protease, it has to be unfolded and translocated into the proteolytic chamber to be degraded. Some proteases appear to be promiscuous, degrading substrates with poorly defined targeting signals, which suggests that selectivity may be controlled at additional levels. Here we compare the abilities of representatives from all classes of ATP-dependent proteases to unfold a model substrate protein and find that the unfolding abilities range over more than 2 orders of magnitude. We propose that these differences in unfolding abilities contribute to the fates of substrate proteins and may act as a further layer of selectivity during protein destruction.

Publication types

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

MeSH terms

  • ATP-Dependent Proteases / chemistry
  • Adenosine Triphosphate / chemistry*
  • Bacillus / enzymology*
  • Bacterial Proteins
  • Biochemistry / methods
  • Dose-Response Relationship, Drug
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Kinetics
  • Protease La / chemistry
  • Protein Binding
  • Protein Denaturation
  • Protein Folding
  • Protein Structure, Tertiary
  • Ribonucleases / chemistry
  • Thermodynamics


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Adenosine Triphosphate
  • Ribonucleases
  • Bacillus amyloliquefaciens ribonuclease
  • ATP-Dependent Proteases
  • FtsH protein, E coli
  • Lon protein, E coli
  • Protease La