Specific cleavage of beta-amyloid peptides by a metallopeptidase from Xenopus laevis skin secretions.
Dactylysin (EC 3.5.24.60) is a metalloendopeptidase first isolated from the skin granular gland secretions of Xenopus laevis. This peptidase hydrolyzes bonds on the amino-terminus of singlets and between doublets of hydrophobic amino acids and was considered to play a role in the in vivo inactivation of biologically active regulatory peptides. Here, we show that dactylysin has also the ability to cleave human beta[1-40]-amyloid peptide and related peptides. Cleavage of the wild type beta[1-40]-amyloid peptide form, and to a lesser extent Flemish and Dutch mutants, occurred predominantly at the His14-Glu15 bond. We demonstrate that frog skin exudate contains a full-length amyloid protein precursor detected by immunochemical cross-reactivity with monoclonal antibody against C-terminal human amyloid protein precursor. The possibility that dactylysin, might be involved in normal catabolism of beta amyloid peptide of Xenopus laevis is discussed.
Clamagirand
Christine
C
Laboratoire de Biochimie des Signaux Régulateurs Cellulaires et Moléculaires, Unité Mixte de Recherche 7631 du Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, Paris, France. clamag@ccr.jussieu.fr
Joulie
Catherine
C
Panchal
Maï
M
Sekhri
Redha
R
Hanquez
Chantal
C
Cohen
Paul
P
Rholam
Mohamed
M
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D012634:Bodily Secretions / Q000201:enzymology*; D006801:Humans; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D029867:Xenopus Proteins / Q000302:isolation & purification / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; D011480:Protease Inhibitors; D029867:Xenopus Proteins; C078592:amyloid beta-protein (1-40); D008666:Metalloendopeptidases; C491278:dactylysin, Xenopus; D015032:Zinc