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.
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
Christine
C
Clamagirand
Catherine
C
Joulie
Maï
M
Panchal
Redha
R
Sekhri
Chantal
C
Hanquez
Paul
P
Cohen
Mohamed
M
Rholam
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