title: ILQINS hexapeptide, identified in lysozyme left-handed helical ribbons and nanotubes, forms right-handed helical ribbons and crystals.
abstract: Amyloid fibrils are implicated in over 20 neurodegenerative diseases. The mechanisms of fibril structuring and formation are not only of medical and biological importance but are also relevant for material science and nanotechnologies due to the unique structural and physical properties of amyloids. We previously found that hen egg white lysozyme, homologous to the disease-related human lysozyme, can form left-handed giant ribbons, closing into nanotubes. By using matrix-assisted laser desorption ionization mass spectrometry analysis, we here identify a key component of such structures: the ILQINS hexapeptide. By combining atomic force microscopy and circular dichorism, we find that this fragment, synthesized by solid-phase peptide synthesis, also forms fibrillar structures in water at pH 2. However, all fibrillar structures formed possess an unexpected right-handed twist, a rare chirality within the corpus of amyloid experimental observations. We confirm by small- and wide-angle X-ray scattering and molecular dynamics simulations that these fibrils are composed of conventional left-handed β-sheets, but that packing stresses between adjacent sheets create this twist of unusual handedness. We also show that the right-handed fibrils represent a metastable state toward β-sheet-based microcrystals formation.
authors.affiliation: Food & Soft Materials, Department of Health Science & Technology, ETH Zurich , Schmelzbergstrasse 9, LFO, E23, 8092 Zürich, Switzerland.
authors.forename: Cecile
authors.initials: C
authors.lastname: Lara
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Reynolds
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Berryman
authors.forename: Anqiu
authors.initials: A
authors.lastname: Xu
authors.forename: Afang
authors.initials: A
authors.lastname: Zhang
authors.forename: Raffaele
authors.initials: R
authors.lastname: Mezzenga
mesh_terms: D000595:Amino Acid Sequence; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013696:Temperature
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D009113:Muramidase