Abstract |
Oculopharyngeal muscular dystrophy is a late-onset disease caused by an elongation of a natural 10-alanine segment within the N-terminal domain of the nuclear poly(A)-binding protein 1 (PABPN1) to maximally 17 alanines. The disease is characterized by intranuclear deposits consisting primarily of PABPN1. In previous studies, we could show that the N-terminal domain of PABPN1 forms amyloid-like fibrils. Here, we analyze fibril formation of full-length PABPN1. Unexpectedly, fibril formation was independent of the presence of the alanine segment. With regard to fibril formation kinetics and resistance against denaturants, fibrils formed by full-length PABPN1 had completely different properties from those formed by the N-terminal domain. Fourier transformed infrared spectroscopy and limited proteolysis showed that fibrillar PABPN1 has a structure that differs from native PABPN1. Circumstantial evidence is presented that the C-terminal domain is involved in fibril formation.
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Authors | Reno Winter, Uwe Kühn, Gerd Hause, Elisabeth Schwarz |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 287
Issue 27
Pg. 22662-71
(Jun 29 2012)
ISSN: 1083-351X [Electronic] United States |
PMID | 22570486
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Poly(A)-Binding Protein II
- Recombinant Proteins
- Alanine
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Topics |
- Alanine
(chemistry)
- Amyloidosis
(genetics, metabolism)
- Escherichia coli
(genetics)
- Humans
- Muscular Dystrophy, Oculopharyngeal
(genetics, metabolism)
- Poly(A)-Binding Protein II
(chemistry, genetics, metabolism)
- Protein Folding
- Protein Structure, Tertiary
- Proteostasis Deficiencies
(genetics, metabolism)
- Recombinant Proteins
(chemistry, genetics, metabolism)
- Solubility
- Spectrophotometry, Infrared
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