TY - JOUR
T1 - The Role of Protein Sequence and Amino Acid Composition in Amyloid Formation: Scrambling and Backward Reading of IAPP Amyloid Fibrils
AU - Sabaté, Raimon
AU - Espargaró, Alba
AU - de Groot, Natalia S.
AU - Valle-Delgado, Juan José
AU - Fernàndez-Busquets, Xavier
AU - Ventura, Salvador
PY - 2010/11/26
Y1 - 2010/11/26
N2 - The specific functional structure of natural proteins is determined by the way in which amino acids are sequentially connected in the polypeptide. The tight sequence/structure relationship governing protein folding does not seem to apply to amyloid fibril formation because many proteins without any sequence relationship have been shown to assemble into very similar β-sheet-enriched structures. Here, we have characterized the aggregation kinetics, seeding ability, morphology, conformation, stability, and toxicity of amyloid fibrils formed by a 20-residue domain of the islet amyloid polypeptide (IAPP), as well as of a backward and scrambled version of this peptide. The three IAPP peptides readily aggregate into ordered, β-sheet-enriched, amyloid-like fibrils. However, the mechanism of formation and the structural and functional properties of aggregates formed from these three peptides are different in such a way that they do not cross-seed each other despite sharing a common amino acid composition. The results confirm that, as for globular proteins, highly specific polypeptide sequential traits govern the assembly pathway, final fine structure, and cytotoxic properties of amyloid conformations. © 2010 Elsevier Ltd.
AB - The specific functional structure of natural proteins is determined by the way in which amino acids are sequentially connected in the polypeptide. The tight sequence/structure relationship governing protein folding does not seem to apply to amyloid fibril formation because many proteins without any sequence relationship have been shown to assemble into very similar β-sheet-enriched structures. Here, we have characterized the aggregation kinetics, seeding ability, morphology, conformation, stability, and toxicity of amyloid fibrils formed by a 20-residue domain of the islet amyloid polypeptide (IAPP), as well as of a backward and scrambled version of this peptide. The three IAPP peptides readily aggregate into ordered, β-sheet-enriched, amyloid-like fibrils. However, the mechanism of formation and the structural and functional properties of aggregates formed from these three peptides are different in such a way that they do not cross-seed each other despite sharing a common amino acid composition. The results confirm that, as for globular proteins, highly specific polypeptide sequential traits govern the assembly pathway, final fine structure, and cytotoxic properties of amyloid conformations. © 2010 Elsevier Ltd.
KW - Amyloid formation
KW - Islet amyloid polypeptide
KW - Protein aggregation
KW - Protein sequence
KW - Retro proteins
U2 - https://doi.org/10.1016/j.jmb.2010.09.052
DO - https://doi.org/10.1016/j.jmb.2010.09.052
M3 - Article
VL - 404
SP - 337
EP - 352
ER -