A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy.

Ritu Khurana; Cristian Ionescu-Zanetti; Maighdlin Pope; Jie Li; Liza Nielson; Marina Ramírez-Alvarado; Lynn Regan; Anthony L Fink; Sue A Carter

doi:10.1016/s0006-3495(03)74550-0

PubMed · 12885658

A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy.

Ritu Khurana·Cristian Ionescu-Zanetti·Maighdlin Pope·Jie Li·Liza Nielson·Marina Ramírez-Alvarado·Lynn Regan·Anthony L Fink·Sue A Carter

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Abstract

Based on atomic force microscopy analysis of the morphology of fibrillar species formed during fibrillation of alpha-synuclein, insulin, and the B1 domain of protein G, a previously described model for the assembly of amyloid fibrils of immunoglobulin light-chain variable domains is proposed as a general model for the assembly of protein fibrils. For all of the proteins studied, we observed two or three fibrillar species that vary in diameter. The smallest, protofilaments, have a uniform height, whereas the larger species, protofibrils and fibrils, have morphologies that are indicative of multiple protofilaments intertwining. In all cases, protofilaments intertwine to form protofibrils, and protofibrils intertwine to form fibrils. We propose that the hierarchical assembly model describes a general mechanism of assembly for all amyloid fibrils.

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Amyloid Binding Sites Crystallography Dimerization Immunoglobulin G Insulin Microscopy, Atomic Force Models, Chemical Models, Molecular Nerve Tissue Proteins Protein Binding Protein Conformation Protein Structure, Tertiary Synucleins alpha-Synuclein Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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Ritu Khurana, Cristian Ionescu-Zanetti, Maighdlin Pope, Jie Li, Liza Nielson, Marina Ramírez-Alvarado, Lynn Regan, Anthony L Fink, Sue A Carter. 2003. A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy.. https://doi.org/10.1016/s0006-3495(03)74550-0

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