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 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.
Fändrich
Marcus
M
Institut für Molekulare Biotechnologie (IMB), Beutenbergstrasse 11, Postfach 100 813, D-07708 Jena, Germany. fandrich@imb-jena.de
Zandomeneghi
Giorgia
G
Krebs
Mark R H
MR
Kittler
Marlis
M
Buder
Katrin
K
Rossner
Angela
A
Heinemann
Stefan H
SH
Dobson
Christopher M
CM
Diekmann
Stephan
S
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D001059:Apoproteins / Q000737:chemistry*; D006736:Horses; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009211:Myoglobin / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D000682:Amyloid; D001059:Apoproteins; D009211:Myoglobin; C010857:apomyoglobin