In order to understand the role of tryptophan in the mechanisms of fibrils formation, the ability of a series of analogs of the residue 7-18 span of myoglobin to form amyloid-like fibrils was investigated. Alternatively one or both tryptophans were substituted with alanine and leucine, to determine the contribution of hydrophobicity and aromaticity. The scale of aggregation propensity of the peptides determined indicates that tryptophan is crucial for the amyloidogenic process. Since the rare tryptophan residue is generally engaged in structural roles in proteins, or when exposed serves as binding sites, we surmise that its exposure in the amyloidogenic fragments allows for intermolecular clustering with residues from other molecules leading to the formation of amyloid aggregates.

The role of tryptophan in protein fibrillogenesis: relevance of Trp7 and Trp14 to the amyloidogenic properties of myoglobin

DE FRANCESCHI, GIORGIA;FRARE, ERICA;FONTANA, ANGELO;POLVERINO DE LAURETO, PATRIZIA
2012

Abstract

In order to understand the role of tryptophan in the mechanisms of fibrils formation, the ability of a series of analogs of the residue 7-18 span of myoglobin to form amyloid-like fibrils was investigated. Alternatively one or both tryptophans were substituted with alanine and leucine, to determine the contribution of hydrophobicity and aromaticity. The scale of aggregation propensity of the peptides determined indicates that tryptophan is crucial for the amyloidogenic process. Since the rare tryptophan residue is generally engaged in structural roles in proteins, or when exposed serves as binding sites, we surmise that its exposure in the amyloidogenic fragments allows for intermolecular clustering with residues from other molecules leading to the formation of amyloid aggregates.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2488518
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