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

Autor: de Freitas MS; Leibniz-Institut für Molekulare Pharmakologie, Department NMR-Supported Structural Biology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany; Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica Leopoldo de Meis, Centro Nacional de Biologia Estrutural e Bioimagem, Av. Carlos Chagas Filho 373, Rio de Janeiro, Brazil., Rezaei Araghi R; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Brandenburg E; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Leiterer J; BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany., Emmerling F; BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany., Folmert K; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Gerling-Driessen UIM; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Bardiaux B; Institut Pasteur, Unité de Bioinformatique Structurale, CNRS UMR 3528, 75015 Paris, France., Böttcher C; Freie Universität Berlin, Research Center for Electron Microscopy, Fabeckstrasse 36a, 14195 Berlin, Germany., Pagel K; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany., Diehl A; Leibniz-Institut für Molekulare Pharmakologie, Department NMR-Supported Structural Biology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany., Berlepsch HV; Freie Universität Berlin, Research Center for Electron Microscopy, Fabeckstrasse 36a, 14195 Berlin, Germany., Oschkinat H; Leibniz-Institut für Molekulare Pharmakologie, Department NMR-Supported Structural Biology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany. Electronic address: oschkinat@fmp-berlin.de., Koksch B; Freie Universität Berlin, Department of Chemistry and Biochemistry, Takustrasse 3, 14195 Berlin, Germany. Electronic address: beate.koksch@fu-berlin.de.
Jazyk: angličtina
Zdroj: Journal of structural biology [J Struct Biol] 2018 Sep; Vol. 203 (3), pp. 263-272. Date of Electronic Publication: 2018 May 29.
DOI: 10.1016/j.jsb.2018.05.009
Abstrakt: 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.
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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