title: Apomyoglobin reveals a random-nucleation mechanism in amyloid protofibril formation.
abstract: 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.
authors.affiliation: Institut für Molekulare Biotechnologie (IMB), Beutenbergstrasse 11, Postfach 100 813, D-07708 Jena, Germany. fandrich@imb-jena.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
authors.forename: Giorgia
authors.initials: G
authors.lastname: Zandomeneghi
authors.forename: Mark R H
authors.initials: MR
authors.lastname: Krebs
authors.forename: Marlis
authors.initials: M
authors.lastname: Kittler
authors.forename: Katrin
authors.initials: K
authors.lastname: Buder
authors.forename: Angela
authors.initials: A
authors.lastname: Rossner
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Stephan
authors.initials: S
authors.lastname: Diekmann
mesh_terms: 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
chemical_list: D000682:Amyloid; D001059:Apoproteins; D009211:Myoglobin; C010857:apomyoglobin