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Polyalanine-independent conformational conversion of nuclear poly(A)-binding protein 1 (PABPN1).

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.
AuthorsReno Winter, Uwe Kühn, Gerd Hause, Elisabeth Schwarz
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 27 Pg. 22662-71 (Jun 29 2012) ISSN: 1083-351X [Electronic] United States
PMID22570486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Poly(A)-Binding Protein II
  • Recombinant Proteins
  • Alanine
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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