Inhibitor‐Mediated Structural Transition in a Minimal Amyloid Model
| Autor: | Ashim Paul, Santu Bera, Petr Král, Phil Mickel, Linda J. W. Shimon, Daniel L. Segal, Zohar A. Arnon, Priyadarshi Chakraborty, Ehud Gazit |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Amyloid Supramolecular chemistry Beta sheet Peptide Crystal structure 02 engineering and technology Depsides Catalysis chemistry.chemical_compound 03 medical and health sciences mental disorders Molecule Humans Particle Size 030304 developmental biology chemistry.chemical_classification 0303 health sciences Dipeptide Amyloid beta-Peptides General Chemistry General Medicine 021001 nanoscience & nanotechnology chemistry Cinnamates Helix Biophysics 0210 nano-technology |
| Zdroj: | Angewandte Chemie. 134 |
| ISSN: | 1521-3757 0044-8249 |
| DOI: | 10.1002/ange.202113845 |
| Popis: | Despite the fundamental clinical importance of amyloid fibril formation, its mechanism is still enigmatic. Crystallography of minimal amyloid models was a milestone in the understanding of the architecture and biological activities of amyloid fibers. However, the crystal structure of ultimate dipeptide-based amyloids is not yet reported. Herein, we present the crystal structure of a typical amyloid-forming minimal dipeptide, Ac-Phe-Phe-NH2 (Ac-FF-NH2 ), showing a canonical β-sheet structure at the atomic level. The simplicity of the structure helped in investigating amyloid-inhibition using crystallography, never previously reported for larger peptide models. Interestingly, in the presence of an inhibitor, the supramolecular packing of Ac-FF-NH2 molecules rearranged into a supramolecular 2-fold helix (21 helix). This study promotes our understanding of the mechanism of amyloid formation and of the structural transitions that occur during the inhibition process in a most fundamental model. |
| Databáze: | OpenAIRE |
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