ATP-dependent proteases in prokaryotic and eukaryotic cells

Semin Cell Biol. 1990 Dec;1(6):423-32.


The energy-requirement for intracellular proteolysis is due largely to the involvement of large multimeric proteases whose function requires ATP hydrolysis. The best-studied such enzyme is protease La from E coli. This tetrameric protease is inhibited in vivo until the binding of an unfolded protein allostericically activates its peptidase and ATPase functions. This mechanism and tight transcriptional regulation prevent non-specific or excessive proteolysis. E. coli contains another ATP-hydrolyzing protease, Ti (Clp), which contains distinct ATPase and proteolytic subunits. Enzymes homologous to La and Ti exist in mitochondria and chloroplasts. In eukaryotic cells, a major neutral proteolytic activity is the 650 kDa proteasome. This multicatalytic structure can function as an ATP-dependent protease or as part of the ATP-dependent complex that degrades ubiquitinated proteins. In mammalian muscle this 1300 kDa complex is formed by an ATP-dependent association of the proteasome with another ATP-dependent protease complex, multipain. Much remains to be learned about the physiological roles and mechanisms of these novel proteases.

Publication types

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

MeSH terms

  • ATP-Dependent Proteases
  • Adenosine Triphosphatases*
  • Adenosine Triphosphate / physiology*
  • Animals
  • Cysteine Endopeptidases / physiology
  • Endopeptidase Clp
  • Endopeptidases / metabolism
  • Endopeptidases / physiology*
  • Enzyme Activation
  • Escherichia coli / enzymology
  • Eukaryotic Cells / enzymology
  • Heat-Shock Proteins*
  • Multienzyme Complexes / physiology
  • Organelles / enzymology
  • Prokaryotic Cells / enzymology
  • Proteasome Endopeptidase Complex
  • Serine Endopeptidases / metabolism*
  • Serine Endopeptidases / physiology


  • Heat-Shock Proteins
  • Multienzyme Complexes
  • Adenosine Triphosphate
  • Endopeptidases
  • ATP-Dependent Proteases
  • Serine Endopeptidases
  • Endopeptidase Clp
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • ubiquitin-Nalpha-protein hydrolase
  • Adenosine Triphosphatases