title: Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self-Assembly of Distinct Amyloid Structures.
abstract: Polymorphism is a common property of amyloid fibers that complicates their detailed structural and functional studies. Here we report experiments illustrating the chemical principles that enable the formation of amyloid polymorphs with distinct stoichiometric composition. Using appropriate covalent tethering we programmed self-assembly of a model peptide corresponding to the [20-41] fragment of human β2-microglobulin into fibers with either trimeric or dimeric amyloid cores. Using a set of biophysical and biochemical methods we demonstrated their distinct structural, morphological, and templating properties. Furthermore, we showed that supramolecular approaches in which the peptide is modified with bulky substituents can also be applied to modulate the formation of different fiber polymorphs. Such strategies, when applied to disease-related peptides and proteins, will greatly help in the evaluation of the biological properties of structurally distinct amyloids.
authors.affiliation: ISIS (Institut de Science et d'Ingénierie Supramoléculaires) and, icFRC (International Center for Frontier Research in Chemistry), University of Strasbourg, CNRS-, UMR 7006, 8 allée Gaspard Monge, 67083, Strasbourg, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Ruiz
authors.affiliation: ISIS (Institut de Science et d'Ingénierie Supramoléculaires) and, icFRC (International Center for Frontier Research in Chemistry), University of Strasbourg, CNRS-, UMR 7006, 8 allée Gaspard Monge, 67083, Strasbourg, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Boehringer
authors.affiliation: ISIS (Institut de Science et d'Ingénierie Supramoléculaires) and, icFRC (International Center for Frontier Research in Chemistry), University of Strasbourg, CNRS-, UMR 7006, 8 allée Gaspard Monge, 67083, Strasbourg, France.
authors.forename: Marcel
authors.initials: M
authors.lastname: Grogg
authors.affiliation: Membrane Biophysics and NMR, Institute of Chemistry, University of Strasbourg, CNRS-, UMR 7177, 4 rue Blaise Pascal, 67008, Strasbourg, France.
authors.forename: Jésus
authors.initials: J
authors.lastname: Raya
authors.affiliation: Laboratory of Bioelectrochemistry and Spectroscopy, University of Strasbourg, CNRS-, UMR 7140, 1 rue Blaise Pascal, 67070, Strasbourg, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Schirer
authors.affiliation: Department of Integrated Structural Biology, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM-U964, University of Strasbourg, CNRS-, UMR 7104, 1 rue Laurent Fries, 67404, Illkirch, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Crucifix
authors.affiliation: Laboratory of Bioelectrochemistry and Spectroscopy, University of Strasbourg, CNRS-, UMR 7140, 1 rue Blaise Pascal, 67070, Strasbourg, France.
authors.forename: Petra
authors.initials: P
authors.lastname: Hellwig
authors.affiliation: Department of Integrated Structural Biology, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM-U964, University of Strasbourg, CNRS-, UMR 7104, 1 rue Laurent Fries, 67404, Illkirch, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schultz
authors.affiliation: ISIS (Institut de Science et d'Ingénierie Supramoléculaires) and, icFRC (International Center for Frontier Research in Chemistry), University of Strasbourg, CNRS-, UMR 7006, 8 allée Gaspard Monge, 67083, Strasbourg, France.
authors.forename: Vladimir
authors.identifier: 0000-0002-7865-1044
authors.initials: V
authors.lastname: Torbeev
mesh_terms: D000682:Amyloid / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D000682:Amyloid
keywords: aggregation; amyloid-beta peptides; protein design; protein folding; self-assembly