Protein processing mechanisms: from angiotensin-converting enzyme to Alzheimer's disease.
Angiotensin-converting enzyme (ACE) and the Alzheimer's disease amyloid precursor protein are two examples of membrane-bound proteins that are released in a soluble form by a post-translational proteolytic cleavage event involving a secretase. Site-specific antibodies and matrix-assisted laser desorption ionization-time-of-flight ('MALDI-TOF') MS have been used to map the secretase cleavage site in somatic ACE to Arg-1203/Ser-1204, 24 residues proximal to the membrane-anchoring domain. Trypsin, which can solubilize ACE from the membrane, cleaves the protein at the same site. The use of structurally related hydroxamic acid-based zinc metalloproteinase inhibitors indicate that tumour necrosis factor-alpha convertase, a member of the ADAMs ('a disintegrin and metalloproteinase') family of proteins, is not involved in the proteolytic release of ACE, or in the constitutive or regulated alpha-secretase release of the amyloid precursor protein from a human neuronal cell line.
Hooper
N M
NM
Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K. n.m.hooper@leeds.ac.uk
Turner
A J
AJ
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D019483:Disintegrins / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D019483:Disintegrins; D006877:Hydroxamic Acids; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; D014357:Trypsin; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; D015032:Zinc