Many major degenerative disorders are associated with the formation of amyloid fibrils by proteins and peptides. Recent studies have extended the repertoire of amyloidogenic building blocks to non-proteinaceous entities, including amino acids and nucleobases. Here, based on the high propensity of tryptophan-containing proteins and peptides to form amyloid fibrils, we explored the self-assembly profile of this amino acid. We discovered that tryptophan forms fibrillary assemblies with a diameter of 15–75 nm. These fibrils bind the thioflavin T amyloid-specific dye and show a typical spectrum of amyloid proteins upon binding. Furthermore, the assemblies show significant cytotoxicity triggered by an apoptosis mechanism, similar to that known for amyloids. As a control, the non-amyloidogenic amino acid alanine was used under the same conditions and did not show any toxicity. Molecular dynamics simulations were used to explore the possible growth mechanism, molecular organization, and stability of tryptophan amyloidal fibrils. Taken together, we provide further extension to the amyloid hypothesis and additional indication for a knwon mechanism of toxicity for both amyloid-associated and metabolic disorders.
- amino acids
- metabolic disorders
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