title: Exploring the sequence-structure relationship for amyloid peptides.
abstract: Amyloid fibril formation is associated with misfolding diseases, as well as fulfilling a functional role. The cross-β molecular architecture has been reported in increasing numbers of amyloid-like fibrillar systems. The Waltz algorithm is able to predict ordered self-assembly of amyloidogenic peptides by taking into account the residue type and position. This algorithm has expanded the amyloid sequence space, and in the present study we characterize the structures of amyloid-like fibrils formed by three peptides identified by Waltz that form fibrils but not crystals. The structural challenge is met by combining electron microscopy, linear dichroism, CD and X-ray fibre diffraction. We propose structures that reveal a cross-β conformation with 'steric-zipper' features, giving insights into the role for side chains in peptide packing and stability within fibrils. The amenity of these peptides to structural characterization makes them compelling model systems to use for understanding the relationship between sequence, self-assembly, stability and structure of amyloid fibrils.
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Morris
authors.forename: Alison
authors.initials: A
authors.lastname: Rodger
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hicks
authors.forename: Maya
authors.initials: M
authors.lastname: Debulpaep
authors.forename: Joost
authors.initials: J
authors.lastname: Schymkowitz
authors.forename: Frederic
authors.initials: F
authors.lastname: Rousseau
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments