Deciphering the Structure, Growth and Assembly of Amyloid-Like Fibrils Using High-Speed Atomic Force Microscopy
Open Access
- 8 October 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (10), e13240
- https://doi.org/10.1371/journal.pone.0013240
Abstract
Formation of fibrillar structures of proteins that deposit into aggregates has been suggested to play a key role in various neurodegenerative diseases. However mechanisms and dynamics of fibrillization remains to be elucidated. We have previously established that lithostathine, a protein overexpressed in the pre-clinical stages of Alzheimer's disease and present in the pathognomonic lesions associated with this disease, form fibrillar aggregates after its N-terminal truncation. In this paper we visualized, using high-speed atomic force microscopy (HS-AFM), growth and assembly of lithostathine protofibrils under physiological conditions with a time resolution of one image/s. Real-time imaging highlighted a very high velocity of elongation. Formation of fibrils via protofibril lateral association and stacking was also monitored revealing a zipper-like mechanism of association. We also demonstrate that, like other amyloid ß peptides, two lithostathine protofibrils can associate to form helical fibrils. Another striking finding is the propensity of the end of a growing protofibril or fibril to associate with the edge of a second fibril, forming false branching point. Taken together this study provides new clues about fibrillization mechanism of amyloid proteins.This publication has 51 references indexed in Scilit:
- Aβ(1-40) Fibril Polymorphism Implies Diverse Interaction Patterns in Amyloid FibrilsJournal of Molecular Biology, 2009
- Branching in Amyloid Fibril GrowthBiophysical Journal, 2009
- Stepwise dynamics of epitaxially growing single amyloid fibrilsProceedings of the National Academy of Sciences of the United States of America, 2008
- Atomic structures of amyloid cross-β spines reveal varied steric zippersNature, 2007
- Insights into the architecture of the Ure2p yeast protein assemblies from helical twisted fibrilsProtein Science, 2006
- Multiple Assembly Pathways Underlie Amyloid-β Fibril PolymorphismsJournal of Molecular Biology, 2005
- Rapid Self-assembly of α-Synuclein Observed by In Situ Atomic Force MicroscopyJournal of Molecular Biology, 2004
- α-Synuclein, Especially the Parkinson's Disease-associated Mutants, Forms Pore-like Annular and Tubular ProtofibrilsJournal of Molecular Biology, 2002
- Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packingThe EMBO Journal, 1999
- Synchrotron X-ray studies suggest that the core of the transthyretin amyloid fibril is a continuous β-sheet helixStructure, 1996