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

TOC_Santos_JStructBiol_pub_069

Fig. 1: Helical wheel representation of RR0

Santos de Freitas, M.; Rezaei Araghi, R.; Brandenburg, E.; Leiterer, J.; Emmerling, F.; Folmert, K.; Gerling-Driessen, U.; Bardiaux, B.; Böttcher, C.; Pagel, K.; Diehl, A.; v. Berlepsch, H.; Oschkinat, H.*; K. Beate* – 2018

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.

Title
The protofilament architecture of a de novo designed coiled coil-based amyloidogenic peptide
Author
Santos de Freitas, M.; Rezaei Araghi, R.; Brandenburg, E.; Leiterer, J.; Emmerling, F.; Folmert, K.; Gerling-Driessen, U.; Bardiaux, B.; Böttcher, C.; Pagel, K.; Diehl, A.; v. Berlepsch, H.; Oschkinat, H.*; K. Beate*
Date
2018
Source(s)
Citation
J. Struct. Biol. 2018, 203, 263–272.
Type
Text
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