In vitro fibril formation from alpha 1-antitrypsin-derived C-terminal peptides.
Fragments from various proteolytically degraded precursor proteins can form beta-amyloid fibrils. We studied, by electron microscopy and quantitative Congo red binding, the ability of three synthetic peptides, corresponding to residues 359-374 (C-36), 370-374 (C-5) and 375-394 (C-20) from the C-terminal part of alpha 1-antitrypsin (AAT) to form beta-amyloid fibrils in vitro. The peptides C-36 and C-5 had a pronounced tendency to form fibrils. C-20 lacked this property, suggesting that residues 359-375 and/or 370-374 are most critical for fibril formation. Native AAT added to peptide 125I-C-36 could bind and form complexes with the peptide, resulting in inhibition of amyloid fibril formation. Moreover, native AAT added to preformed fibrils induced disaggregation of fibrillar structures. The structural rearrangements of AAT that occurred during this 'autointeraction' included polymerization of the serpin, and an increase of its thermal stability. Also, following interaction, an increase (20-40%) of AAT's antielastase activity was noted. The demonstration of an in vitro beta-amyloid fibril formation from the AAT derived C-terminal peptides C-36 and C-5 and its regulation by the intact AAT molecule may have important in vivo implications.
Janciauskiene
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Lund University, Department of Medicine, Malmö University Hospital, Sweden.
Carlemalm
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Eriksson
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D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D003224:Congo Red; D006358:Hot Temperature; D006801:Humans; D008027:Light; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012542:Scattering, Radiation; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D046911:Macromolecular Substances; D010455:Peptides; D000515:alpha 1-Antitrypsin; D003224:Congo Red