Flow-induced alignment of amyloid protofilaments revealed by linear dichroism.
Amyloid fibrils underlying various serious amyloidoses including Alzheimer and prion diseases form characteristic deposits in which linear fibrils with an unbranched and rigid morphology associate laterally or radially, e.g. radial senile amyloid plaques of amyloid beta. To clarify the formation of these high order amyloid deposits, studying the rheology is important. A 22-residue K3 peptide fragment of beta2-microglobulin, a protein responsible for dialysis-related amyloidosis, forms long and homogeneous protofilament-like fibrils in 20% (v/v) 2,2,2-trifluoroethanol and 10 mM HCl (pH approximately 2). Here, using circular dichroism and linear dichroism, we observed the flow-induced alignment of fibrils. Analysis of far- and near-UV linear dichroism spectra suggested that both the net pi-pi* transition moment of the backbone carbonyl group and L(b) transition moment of the Tyr(26) side chain are oriented in parallel to the fibril axis, revealing the structural details of amyloid protofilaments. Moreover, the intensities of flow-induced circular dichroism or linear dichroism signals depended critically on the length and type of fibrils, suggesting that they are useful for detecting and characterizing amyloid fibrils.
Adachi
Rumi
R
Institute for Protein Research, Osaka University and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
Yamaguchi
Kei-ichi
K
Yagi
Hisashi
H
Sakurai
Kazumasa
K
Naiki
Hironobu
H
Goto
Yuji
Y
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D008954:Models, Biological; D008956:Models, Chemical; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D012212:Rheology; D014466:Ultraviolet Rays
D000682:Amyloid; D016229:Amyloid beta-Peptides; D011994:Recombinant Proteins