Water-Soluble -Sheet Models Which Self-Assemble into Fibrillar Structures
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- 作者：Katharina Janek ; Joachim Behlke ; Josef Zipper ; Heinz Fabian ; Yannis Georgalis ; Michael Beyermann ; Michael Bienert ; and Eberhard Krause
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：June 29, 1999
- 年：1999
- 卷：38
- 期：26
- 页码：8246 - 8252
- 全文大小：123K
- 年卷期：v.38,no.26(June 29, 1999)
- ISSN：1520-4995
文摘
Self-assembly of 
-sheet domains resulting in the formation of pathogenic, fibrillar proteinaggregates (amyloids) is a characteristic feature of various medical disorders. These include neurodegenerative diseases, such as Alzheimer's, Huntington's, and Creutzfeldt-Jacob's. A significant problemin studying such aggregation processes is the poor solubility of these -sheet complexes. The presentwork describes water-soluble de novo -sheet peptides which self-assemble into fibrillar structures. Themodel peptides enable studies of the relationship between -sheet stability and association behavior. Thepeptides [DPKGDPKG-(VT)n-GKGDPKPD-NH2, n = 3-8] are composed of a central -sheet-formingdomain (VT-sequence), and N- and C-terminal nonstructured octapeptide sequences which promote watersolubility. Conformational analyses by circular dichroism and Fourier transform infrared spectroscopyindicate the influence of peptide length, D-amino acid substitution, and concentration on the ability of thepeptides to form stable -sheet structures. The association behavior investigated by analytical ultracentrifugation and dynamic light scattering was found to correlate strongly with the stability of a -sheetconformation. Model peptides with n 
6 form stable, water-soluble -sheet complexes with molecularmasses of more than 2000 kDa, which are organized in fibrillar structures. The fibrils examined by CongoRed staining and electron microscopy show some similarities with naturally occurring amyloid fibrils.
-sheet domains resulting in the formation of pathogenic, fibrillar proteinaggregates (amyloids) is a characteristic feature of various medical disorders. These include neurodegenerative diseases, such as Alzheimer's, Huntington's, and Creutzfeldt-Jacob's. A significant problemin studying such aggregation processes is the poor solubility of these -sheet complexes. The presentwork describes water-soluble de novo -sheet peptides which self-assemble into fibrillar structures. Themodel peptides enable studies of the relationship between -sheet stability and association behavior. Thepeptides [DPKGDPKG-(VT)n-GKGDPKPD-NH2, n = 3-8] are composed of a central -sheet-formingdomain (VT-sequence), and N- and C-terminal nonstructured octapeptide sequences which promote watersolubility. Conformational analyses by circular dichroism and Fourier transform infrared spectroscopyindicate the influence of peptide length, D-amino acid substitution, and concentration on the ability of thepeptides to form stable -sheet structures. The association behavior investigated by analytical ultracentrifugation and dynamic light scattering was found to correlate strongly with the stability of a -sheetconformation. Model peptides with n 6 form stable, water-soluble -sheet complexes with molecularmasses of more than 2000 kDa, which are organized in fibrillar structures. The fibrils examined by CongoRed staining and electron microscopy show some similarities with naturally occurring amyloid fibrils.