A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy.
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.
Khurana
Ritu
R
Department of Chemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA. ritukhurana2001@yahoo.com
Ionescu-Zanetti
Cristian
C
Pope
Maighdlin
M
Li
Jie
J
Nielson
Liza
L
Ramírez-Alvarado
Marina
M
Regan
Lynn
L
Fink
Anthony L
AL
Carter
Sue A
SA
D000682:Amyloid / Q000737:chemistry / Q000648:ultrastructure*; D001665:Binding Sites; D003461:Crystallography / Q000379:methods*; D019281:Dimerization; D007074:Immunoglobulin G / Q000737:chemistry / Q000648:ultrastructure*; D007328:Insulin / Q000737:chemistry*; D018625:Microscopy, Atomic Force / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051843:Synucleins; D051844:alpha-Synuclein
D000682:Amyloid; C029152:G-substrate; D007074:Immunoglobulin G; D007328:Insulin; D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein