TY - JOUR
T1 - A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy
AU - Khurana, Ritu
AU - Ionescu-Zanetti, Cristian
AU - Pope, Maighdlin
AU - Li, Jie
AU - Nielson, Liza
AU - Ramirez-Alvarado, Marina
AU - Regan, Lynn
AU - Fink, Anthony L.
AU - Carter, Sue A.
N1 - Funding Information:
This work was supported by grants from the Packard Foundations (to S.A. Carter) and the National Institutes of Health (to A.L. Fink). M. Ramírez-Alvarado is a Human Frontier Science Program postdoctoral fellow.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Based on atomic force microscopy analysis of the morphology of fibrillar species formed during fibrillation of α-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.
AB - Based on atomic force microscopy analysis of the morphology of fibrillar species formed during fibrillation of α-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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U2 - 10.1016/S0006-3495(03)74550-0
DO - 10.1016/S0006-3495(03)74550-0
M3 - Article
C2 - 12885658
AN - SCOPUS:0041343061
SN - 0006-3495
VL - 85
SP - 1135
EP - 1144
JO - Biophysical Journal
JF - Biophysical Journal
IS - 2
ER -