ILQINS Hexapeptide, Identified in Lysozyme Left-Handed Helical Ribbons and Nanotubes, Forms Right-Handed Helical Ribbons and Crystals

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.