ATP-dependent proteases in prokaryotic and eukaryotic cells.
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.
Goldberg
A L
AL
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.
D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000502:physiology; D049071:Endopeptidase Clp; D010450:Endopeptidases / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology; D005057:Eukaryotic Cells / Q000201:enzymology; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes / Q000502:physiology; D015388:Organelles / Q000201:enzymology; D011387:Prokaryotic Cells / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000502:physiology
D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D000255:Adenosine Triphosphate; D010450:Endopeptidases; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C059237:ubiquitin-Nalpha-protein hydrolase; D000251:Adenosine Triphosphatases