The N-end rule pathway for regulated proteolysis: prokaryotic and eukaryotic strategies.
The N-end rule states that the half-life of a protein is determined by the nature of its N-terminal residue. This fundamental principle of regulated proteolysis is conserved from bacteria to mammals. Although prokaryotes and eukaryotes employ distinct proteolytic machineries for degradation of N-end rule substrates, recent findings indicate that they share common principles of substrate recognition. In eukaryotes substrate recognition is mediated by N-recognins, a class of E3 ligases that labels N-end rule substrates via covalent linkage to ubiquitin, allowing the subsequent substrate delivery to the 26S proteasome. In bacteria, the adaptor protein ClpS exhibits homology to the substrate binding site of N-recognin. ClpS binds to the destabilizing N-termini of N-end rule substrates and directly transfers them to the ClpAP protease.
Mogk
Axel
A
ZMBH, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany.
Schmidt
Ronny
R
Bukau
Bernd
B
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D049071:Endopeptidase Clp / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology; D005057:Eukaryotic Cells / Q000502:physiology*; D063208:Methionyl Aminopeptidases; D009363:Neoplasm Proteins / Q000502:physiology; D011387:Prokaryotic Cells / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*
D002352:Carrier Proteins; C454820:ClpS protein, E coli; D029968:Escherichia coli Proteins; D009363:Neoplasm Proteins; C021081:recognins; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; C483572:ClpP protease, E coli; D049071:Endopeptidase Clp; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease