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

Publication date: Available online 29 May 2018Source: Journal of Structural BiologyAuthor(s): Mônica Santos de Freitas, Raheleh Rezaei Araghi, Enrico Brandenburg, Jork Leiterer, Franziska Emmerling, Kristin Folmert, Ulla I.M. Gerling-Driessen, Benjamin Bardiaux, Christoph Böttcher, Kevin Pagel, Anne Diehl, Hans v. Berlepsch, Hartmut Oschkinat, Beate KokschAbstractAmyloid 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 w...

Source: Journal of Structural Biology - July 11, 2018 Category: Biology Source Type: research