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Effect of oculopharyngeal muscular dystrophy-associated extension of seven alanines on the fibrillation properties of the N-terminal domain of PABPN1

Titelangaben

Lodderstedt, Grit ; Hess, Simone ; Hause, Gerd ; Scheuermann, Till ; Scheibel, Thomas ; Schwarz, Elisabeth:
Effect of oculopharyngeal muscular dystrophy-associated extension of seven alanines on the fibrillation properties of the N-terminal domain of PABPN1.
In: The FEBS Journal. Bd. 274 (2007) Heft 2 . - S. 346-355.
ISSN 1742-4658
DOI: https://doi.org/10.1111/j.1742-4658.2006.05595.x

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that usually manifests itself within the fifth decade. The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N-terminal part of the poly(A)-binding protein 1 (PABPN1) that result in the extension of a 10-alanine segment by up to seven more alanines. In patients, biopsy material displays intranuclear inclusions consisting primarily of PABPN1. Poly l-alanine-dependent fibril formation was studied using the recombinant N-terminal domain of PABPN1. In the case of the protein fragment with the expanded poly l-alanine sequence [N-(+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils serving as seeds. Besides homologous seeds, seeds derived from fibrils of the wild-type fragment (N-WT) also accelerated fibril formation of N-(+7)Ala in a concentration-dependent manner. Seed-induced fibrillation of N-WT was considerably slower than that of N-(+7)Ala. Using atomic force microscopy, differences in fibril morphologies between N-WT and N-(+7)Ala were detected. Furthermore, fibrils of N-WT showed a lower resistance against solubilization with the chaotropic agent guanidinium thiocyanate than those from N-(+7)Ala. Our data clearly reveal biophysical differences between fibrils of the two variants that are likely caused by divergent fibril structures.

Weitere Angaben

Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Keywords: AFM; alanine expansions; amyloid-like; kinetics of fibril formation; OPMD
Institutionen der Universität: Fakultäten
Fakultäten > Fakultät für Ingenieurwissenschaften
Fakultäten > Fakultät für Ingenieurwissenschaften > Lehrstuhl Biomaterialien
Fakultäten > Fakultät für Ingenieurwissenschaften > Lehrstuhl Biomaterialien > Lehrstuhl Biomaterialien - Univ.-Prof. Dr. Thomas Scheibel
Profilfelder > Advanced Fields > Neue Materialien
Profilfelder > Advanced Fields > Molekulare Biowissenschaften
Profilfelder > Advanced Fields > Polymer- und Kolloidforschung
Profilfelder > Emerging Fields > Lebensmittel- und Gesundheitswissenschaften
Profilfelder
Profilfelder > Advanced Fields
Profilfelder > Emerging Fields
Titel an der UBT entstanden: Ja
Themengebiete aus DDC: 600 Technik, Medizin, angewandte Wissenschaften
600 Technik, Medizin, angewandte Wissenschaften > 620 Ingenieurwissenschaften
Eingestellt am: 25 Sep 2015 05:35
Letzte Änderung: 26 Nov 2015 10:51
URI: https://eref.uni-bayreuth.de/id/eprint/19546