Structure, formation and propagation of amyloid fibrils.
Amyloid fibrils have been a critical subject in recent studies of proteins since they are associated with the pathology of more than 20 serious human diseases. Moreover, a variety of proteins and peptides not related to diseases are able to form amyloid fibrils or amyloid-like structures, implying that amyloid formation is a generic property of polypeptides. Although understanding the structure and formation of amyloid fibrils is crucial, due to the extremely high molecular weight and insolubility of amyloid fibrils, most of the conventional techniques available for soluble proteins are not directly applicable to these fibrils. However, structural studies using solid-state NMR have shown that the basic motif of amyloid fibrils is a beta-strand-loop-beta-strand conformation often in a parallel beta-sheet assembly. From the hydrogen/deuterium exchange of amide protons, amyloid fibrils have been shown to be stabilized by an extensive network of hydrogen bonds substantiating beta-sheets. Our approach using total internal reflection fluorescence microscopy combined with thioflavin T, an amyloid-specific fluorescence dye, enabled monitoring fibril growth in real-time at single fibril level. On the basis of these various approaches, increasingly convincing models of amyloid structures, their formation and propagation are emerging.
Goto
Yuji
Y
Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan. ygoto@protein.osaka-u.ac.jp
Yagi
Hisashi
H
Yamaguchi
Keiichi
K
Chatani
Eri
E
Ban
Tadato
T
D000682:Amyloid / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D006801:Humans; D006860:Hydrogen Bonding; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability
D000682:Amyloid