title: Amyloid fibril formation by the CAD domain of caspase-activated DNase.
abstract: Caspase-activated DNase (CAD) is a key protein in the process of apoptosis that degrades DNA through the action of caspases. Its N-terminal region, the CAD domain (CAD-CD), is highly conserved among CAD family proteins and is responsible for the interaction with its inhibitor. We report here that CAD-CD spontaneously aggregates to form amyloid fibrils, without a lag time, under the conditions of low pH (below 4) and the presence of anions. Interestingly, the secondary structure of CAD-CD in the fibril state comprised not only beta-sheet but also alpha-helix, as found in CD, FTIR, and x-ray fiber diffraction experiments. Aromatic side chains have a defined orientation and are in the hydrophobic environment occurring with the CAD-CD fibrillogenesis. These findings provide new insights into the architecture of amyloid fibrils.
authors.affiliation: National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan. k-uegaki@aist.go.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Uegaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Odahara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Harata
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hagihara
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ueyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Noboru
authors.initials: N
authors.lastname: Yumoto
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000838:Anions / Q000737:chemistry; D003851:Deoxyribonucleases / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000682:Amyloid; D000838:Anions; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease