The protofilament architecture of a de novo designed coiled coil-based amyloidogenic peptide

Mônica Santos de Freitas (1, 2, 3) , Raheleh Rezaei Araghi (1) , Enrico Brandenburg (1) , Jork Leiterer (4) , Franziska Emmerling (4) , Kristin Folmert (1) , Ulla Gerling-Driessen (1) , Benjamin Bardiaux (5) , Christoph Böttcher (1) , Kevin Pagel (1) , Anne Diehl (3) , Hans Berlepsch (1) , Hartmut Oschkinat (3, 1) , Beate Koksch (1)

1 Freie Universität Berlin
2 UFRJ - Universidade Federal do Rio de Janeiro [Brasil] = Federal University of Rio de Janeiro [Brazil] = Université fédérale de Rio de Janeiro [Brésil]
3 FMP - Leibniz Forschungsinstitut für Molekulare Pharmakolgie = Leibniz Institute for Molecular Pharmacology [Berlin, Allemagne]
4 BAM Federal Institute for Materials Research and Testing
5 Bioinformatique structurale - Structural Bioinformatics

Amyloid fibrils are polymers formed by proteins under specific conditions and in many cases they are related to pathogenesis, such as Parkinson's and Alzheimer's diseases. Their hallmark is the presence of a β-sheet structure. High resolution structural data on these systems as well as information gathered from multiple complementary analytical techniques is needed, from both a fundamental and a pharmaceutical perspective. Here, a previously reported de novo designed, pH-switchable coiled coil-based peptide that undergoes structural transitions resulting in fibril formation under physiological conditions has been exhaustively characterized by transmission electron microscopy (TEM), cryo-TEM, atomic force microscopy (AFM), wide-angle X-ray scattering (WAXS) and solid-state NMR (ssNMR). Overall, a unique 2-dimensional carpet-like assembly composed of large coexisiting ribbon-like, tubular and funnel-like structures with a clearly resolved protofilament substructure is observed. Whereas electron microscopy and scattering data point somewhat more to a hairpin model of β-fibrils, ssNMR data obtained from samples with selectively labelled peptides are in agreement with both, hairpin structures and linear arrangements.

Mots clés: Amyloid fibrils; Electron microscopy

Domaines: Sciences du Vivant [q-bio]

Mônica Santos de Freitas, Raheleh Rezaei Araghi, Enrico Brandenburg, Jork Leiterer, Franziska Emmerling, et al.. The protofilament architecture of a de novo designed coiled coil-based amyloidogenic peptide. Journal of Structural Biology, 2018, 203 (3), pp.263-272. ⟨10.1016/j.jsb.2018.05.009⟩. ⟨pasteur-02329917⟩