title: Hydrophobic, aromatic, and electrostatic interactions play a central role in amyloid fibril formation and stability.
abstract: Amyloid-like fibrous crystals formed by the peptide KFFEAAAKKFFE have been previously characterized and provide an ideal model system to examine the importance of specific interactions by introducing specific substitutions. We find that the removal of any phenylalanine residue completely abrogates assembly ability, while charged residues modulate interactions within the structure resulting in alternative fibrillar morphologies. X-ray fiber diffraction analysis reveals that the essential backbone packing of the peptide molecules is maintained, while small changes accommodate differences in side chain size in the variants. We conclude that even very short peptides are adaptable and add to the growing knowledge regarding amyloid polymorphisms. Additionally, this work impacts on our understanding of the importance of residue composition for amyloidogenic peptides, in particular the roles of electrostatic, aromatic, and hydrophobic interactions in amyloid assembly.
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Marshall
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Morris
authors.forename: Deborah
authors.initials: D
authors.lastname: Charlton
authors.forename: Nicola
authors.initials: N
authors.lastname: O'Reilly
authors.forename: Laurence
authors.initials: L
authors.lastname: Lewis
authors.forename: Helen
authors.initials: H
authors.lastname: Walden
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010649:Phenylalanine; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D055672:Static Electricity
chemical_list: D016229:Amyloid beta-Peptides; D010649:Phenylalanine