title: Enhanced Fibril Fragmentation of N-Terminally Truncated and Pyroglutamyl-Modified Aβ Peptides.
abstract: N-terminal truncation and pyroglutamyl (pE) formation are naturally occurring chemical modifications of the Aβ peptide in Alzheimer's disease. We show herein that these two modifications significantly reduce the fibril length and the transition midpoint of thermal unfolding of the fibrils, but they do not substantially perturb the fibrillary peptide conformation. This observation implies that the N terminus of the unmodified peptide protects Aβ fibrils against mechanical stress and fragmentation and explains the high propensity of pE-modified peptides to form small and particularly toxic aggregates.
authors.affiliation: Institute for Pharmaceutical Biotechnologie, Ulm University, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wulff
authors.affiliation: Institute of Physics, Martin Luther University Halle-Wittenberg, Betty-Heimann-Strasse 7, 06120, Halle (Saale), Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Probiodrug AG, Biocenter, Weinbergweg 22, 06120, Halle (Saale), Germany.|Nomad Bioscience GmbH, Biocenter, Weinbergweg 22, 06120, Halle (Saale), Germany.
authors.forename: Anka
authors.initials: A
authors.lastname: Thümmler
authors.affiliation: Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, NH-8, Ajmer-, 305801, Rajasthan, India.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Yadav
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstrasse 11a, 07745, Jena, Germany.
authors.forename: Liesa
authors.initials: L
authors.lastname: Heinrich
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstrasse 11a, 07745, Jena, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knüpfer
authors.affiliation: Department of Drug Design and Target Validation MWT Halle/Saale, Fraunhofer Institute for Cell Therapy and Immunology IZI Leipzig, Biocenter, Weinbergweg 22, 06120, Halle (Saale), Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Schlenzig
authors.affiliation: Service Unit for Mass Spectrometry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120, Halle (Saale), Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Schierhorn
authors.affiliation: Department of Drug Design and Target Validation MWT Halle/Saale, Fraunhofer Institute for Cell Therapy and Immunology IZI Leipzig, Biocenter, Weinbergweg 22, 06120, Halle (Saale), Germany.
authors.forename: Jens-Ulrich
authors.initials: JU
authors.lastname: Rahfeld
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstrasse 11a, 07745, Jena, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Horn
authors.affiliation: Institute of Physics, Martin Luther University Halle-Wittenberg, Betty-Heimann-Strasse 7, 06120, Halle (Saale), Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
authors.affiliation: Department of Drug Design and Target Validation MWT Halle/Saale, Fraunhofer Institute for Cell Therapy and Immunology IZI Leipzig, Biocenter, Weinbergweg 22, 06120, Halle (Saale), Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.affiliation: Institute for Pharmaceutical Biotechnologie, Ulm University, Helmholtzstrasse 8/1, 89081, Ulm, Germany. marcus.faendrich@uni-ulm.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D016229:Amyloid beta-Peptides; D011761:Pyrrolidonecarboxylic Acid
keywords: Alzheimer's disease; amyloids; covalent protein modifications; peptide aggregation; protein folding