CLAC binds to amyloid beta peptides through the positively charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils
Autor: | Yuko Matsuo, Tadafumi Hashimoto, Yoshihide Osada, Tomoko Wakabayashi, Takeshi Iwatsubo, Akiko Nishimura |
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Rok vydání: | 2004 |
Předmět: |
Time Factors
Protein Conformation Immunoblotting Molecular Sequence Data Static Electricity Sodium Chloride Transfection Biochemistry Models Biological Cell Line Humans Trypsin Senile plaques Amino Acid Sequence Benzothiazoles Molecular Biology Collagen type chemistry.chemical_classification Amyloid beta-Peptides Dose-Response Relationship Drug Sequence Homology Amino Acid Heparin Temperature Cell Biology DNA Non-Fibrillar Collagens Amyloid fibril In vitro Amyloid β peptide Amino acid Protein Structure Tertiary Microscopy Electron Thiazoles Spectrometry Fluorescence chemistry Culture Media Conditioned Mutation Collagen Triple helix Protein Binding |
Zdroj: | The Journal of biological chemistry. 280(9) |
ISSN: | 0021-9258 |
Popis: | CLAC (collagenous Alzheimer amyloid plaque component) is a proteolytic fragment derived from a novel membrane-bound collagen, CLAC-P/collagen type XXV, that deposits in senile plaques associated with amyloid beta peptides (Abeta) in the brains of patients with Alzheimer's disease. We previously showed that CLAC binds to the fibrillized form of Abeta in vitro, although the mechanism and the subdomains that mediate interaction of CLAC with Abeta as well as the effect of binding of CLAC on amyloid fibril formation remain unknown. Here we show that the collagenous domain 1 of CLAC, which is rich in positively charged amino acid residues, mediates its interaction with Abeta and that this binding is mediated by an electrostatic interaction and requires formation of the triple helix structure of CLAC. The soluble form of CLAC purified from the media of cells transfected with CLAC-P inhibited fibrillization of Abeta in vitro, especially in its elongation phase. These results suggest the anti-amyloidogenic roles of CLAC in the pathophysiology of Alzheimer's disease. |
Databáze: | OpenAIRE |
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