Peptides corresponding to gelsolin derived amyloid of the finnish type (AGelFIN) adopt two distinct forms in solution of which only one can polymerize into amyloid fibrils and form complexes with apoE.
Familial amyloidosis of the Finnish type is caused by a point mutation at position 187 of gelsolin. The mutation generates a proteolytic fragment, which forms amyloid fibrils in vivo. In the present study we have elucidated the aggregation properties of synthetic peptides corresponding to the wild type and mutated gelsolin fragments. We show by high performance size exclusion chromatography and mass spectrometry that a part of these peptides polymerize with an increase in incubation time, while a portion of the same peptide can adopt a soluble, non-polymerizing structure. Peptides that remain soluble are in their monomeric stage, while the polymerizing peptides prefer a dimerized intermediate stage. We also show that the initialform of these peptides in the solution dramatically influence their capability to interact with amlyloid associated proteins, such as apolipoprotein E. Our results indicate that the amyloidogenic fragment of gelsolin can adopt two distinct forms, of which only one can form amyloid fibrils in vitro.
Fadika
Gibril O
GO
Baumann
Marc
M
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D008854:Microscopy, Electron; D009454:Neurofibrils / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers; D011485:Protein Binding; D012995:Solubility; D020349:Surface Plasmon Resonance
D000682:Amyloid; D001057:Apolipoproteins E; D004220:Disulfides; D010446:Peptide Fragments; D011108:Polymers; C103598:amyloid AGel protein, human