Amyloid fibril formation by the CAD domain of caspase-activated DNase.
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.
Uegaki
Koichi
K
National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan. k-uegaki@aist.go.jp
Nakamura
Tsutomu
T
Yamamoto
Hitoshi
H
Kobayashi
Atsuko
A
Odahara
Takayuki
T
Harata
Kazuaki
K
Hagihara
Yoshihisa
Y
Ueyama
Norikazu
N
Yamazaki
Toshio
T
Yumoto
Noboru
N
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
D000682:Amyloid; D000838:Anions; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease