Apomyoglobin reveals a random-nucleation mechanism in amyloid protofibril formation

Protofibrils (PFs) represent the earliest fibrillar species that occur in the course of amyloid fibril formation. Using apomyoglobin, we report here that PFs arise from a multi-step reaction and that they are preceded by an ensemble of non-fibrillar particles (NFPs). These intermediate aggregates en...

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Bibliographic Details
Published in:Acta histochemica 2006-01, Vol.108 (3), p.215-219
Main Authors: Fändrich, Marcus, Zandomeneghi, Giorgia, Krebs, Mark R.H., Kittler, Marlis, Buder, Katrin, Roßner, Angela, Heinemann, Stefan H., Dobson, Christopher M., Diekmann, Stephan
Format: Article
Language:English
Subjects:
Aggregation
Amyloid
Amyloid - chemistry
Amyloid - ultrastructure
Animals
Apomyoglobin
Apoproteins - chemistry
Horses
Microscopy, Atomic Force
Microscopy, Electron, Transmission
Models, Molecular
Myoglobin - chemistry
Protein Conformation
Protein Folding
Protofibrils
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Summary:Protofibrils (PFs) represent the earliest fibrillar species that occur in the course of amyloid fibril formation. Using apomyoglobin, we report here that PFs arise from a multi-step reaction and that they are preceded by an ensemble of non-fibrillar particles (NFPs). These intermediate aggregates encompass nascent elements of amyloid structure and can act as seeds in PF formation. Taken together with the observation that PFs often protrude from NFPs, our data suggest that PFs form by a random nucleation mechanism in which the polypeptide chains sample many different aggregated conformations. Once the appropriate structural characteristics are acquired, PFs are formed by addition of further polypeptide chains.
ISSN:0065-1281
1618-0372
DOI:10.1016/j.acthis.2006.03.012