ABri peptide associated with familial British dementia forms annular and ring-like protofibrillar structures.
Amyloid plaque deposition involves the aggregation of normally soluble proteins into insoluble amyloid fibrils (fibrillization) and proceeds through intermediates with distinct morphologies, including spherical aggregates, protofibrils, and mature fibrils. Recently, a novel annular protofibril-like intermediate with unique pore-like properties was produced by alpha-synuclein, A beta-Arctic and amylin, which are proteins associated with Parkinson's disease, Alzheimer's disease, and type-II diabetes. The observation of annular structures coupled with size selective channel-like activity by these proteins suggests that these structures may be responsible for vesicle permeability by ion-channel formation. Using atomic force spectroscopy, we report here that the ABri peptide associated with familial British dementia produces similar annular and ring-like protofibril structures during the following sequence of events: spherical aggregates (0.4-1.5 nm height)-->chain-like protofibrils (1.5-2.3 nm height)-->ring-like protofibrils and annular protofibrils (1.5-2.3 nm height). This suggests that ABri fibrillization occurs in a similar fashion to other amyloidogenic proteins and that the annular protofibrillar structures may represent a common amyloid intermediate.
Srinivasan
Rekha
R
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA.
Marchant
Roger E
RE
Zagorski
Michael G
MG
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide; D018625:Microscopy, Atomic Force; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D009419:Nerve Tissue Proteins; D010455:Peptides; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein