Regulation of the 26S proteasome activities by peptides mimicking cleavage products.
The implication of the released peptides in allosteric effects during protein degradation catalyzed by the proteasome is an important question not completely resolved. We present here data showing modulation of 26S proteasome activities by peptides composed of 5 or 6 natural amino acids that mimic the products generated during protein breakdown. Several of these peptides inhibit the chymotrypsin-like activity of the Xenope 26S proteasome whereas its trypsin-like activity is enhanced. The basic peptides produced competitive inhibition of the chymotrypsin-like activity and the acidic peptides, parabolic inhibition involving two different binding sites. Our results are in agreement with a model involving hypothetical non-catalytic sites interacting with effectors to modulate the peptidase activities of the proteasome. They also suggest that allosteric effects may occur in the proteasome during protein degradation.
Laboratoire d'Enzymologie Moléculaire et Fonctionnelle, Département de Biologie Cellulaire, Institut Jacques Monod (UMR 7592), Universities Paris 6 and 7, Tour 43, 2 place Jussieu, 75251 Paris Cedex 05, France.
David
D
Papapostolou
Olivier
O
Coux
Michèle
M
Reboud-Ravaux
D000818:Animals; D002918:Chymotrypsin / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D018716:Molecular Mimicry; D009865:Oocytes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013379:Substrate Specificity; D014357:Trypsin / Q000378:metabolism; D014982:Xenopus laevis
D010455:Peptides; D018698:Glutamic Acid; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D014357:Trypsin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease