title: Amyloid fibril formation from sequences of a natural beta-structured fibrous protein, the adenovirus fiber.
abstract: Amyloid fibrils are fibrous beta-structures that derive from abnormal folding and assembly of peptides and proteins. Despite a wealth of structural studies on amyloids, the nature of the amyloid structure remains elusive; possible connections to natural, beta-structured fibrous motifs have been suggested. In this work we focus on understanding amyloid structure and formation from sequences of a natural, beta-structured fibrous protein. We show that short peptides (25 to 6 amino acids) corresponding to repetitive sequences from the adenovirus fiber shaft have an intrinsic capacity to form amyloid fibrils as judged by electron microscopy, Congo Red binding, infrared spectroscopy, and x-ray fiber diffraction. In the presence of the globular C-terminal domain of the protein that acts as a trimerization motif, the shaft sequences adopt a triple-stranded, beta-fibrous motif. We discuss the possible structure and arrangement of these sequences within the amyloid fibril, as compared with the one adopted within the native structure. A 6-amino acid peptide, corresponding to the last beta-strand of the shaft, was found to be sufficient to form amyloid fibrils. Structural analysis of these amyloid fibrils suggests that perpendicular stacking of beta-strand repeat units is an underlying common feature of amyloid formation.
authors.affiliation: Institut de Biologie Structurale, UMR 5075, CEA-CNRS-UJF, 41 Rue Jules Horowitz, 38027 Grenoble, European Molecular Biology Laboratory, 6 Rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Katerina
authors.initials: K
authors.lastname: Papanikolopoulou
authors.forename: Guy
authors.initials: G
authors.lastname: Schoehn
authors.forename: Vincent
authors.initials: V
authors.lastname: Forge
authors.forename: V Trevor
authors.initials: VT
authors.lastname: Forsyth
authors.forename: Christian
authors.initials: C
authors.lastname: Riekel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Hernandez
authors.forename: Rob W H
authors.initials: RW
authors.lastname: Ruigrok
authors.forename: Anna
authors.initials: A
authors.lastname: Mitraki
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D004396:Coloring Agents / Q000494:pharmacology; D003224:Congo Red / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D014965:X-Rays
chemical_list: D000682:Amyloid; D004396:Coloring Agents; D010455:Peptides; D003224:Congo Red