PMID- 17229142
OWN - NLM
STAT- MEDLINE
DCOM- 20070309
LR  - 20131121
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 274
IP  - 2
DP  - 2007 Jan
TI  - Effect of oculopharyngeal muscular dystrophy-associated extension of seven 
      alanines on the fibrillation properties of the N-terminal domain of PABPN1.
PG  - 346-55
AB  - 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.
FAU - Lodderstedt, Grit
AU  - Lodderstedt G
AD  - Institut fur Biotechnologie, Martin-Luther-Universitat Halle-Wittenberg, Halle, 
      Germany.
FAU - Hess, Simone
AU  - Hess S
FAU - Hause, Gerd
AU  - Hause G
FAU - Scheuermann, Till
AU  - Scheuermann T
FAU - Scheibel, Thomas
AU  - Scheibel T
FAU - Schwarz, Elisabeth
AU  - Schwarz E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Peptides)
RN  - 0 (Poly(A)-Binding Protein I)
RN  - 0 (Recombinant Proteins)
RN  - 25191-17-7 (polyalanine)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/*chemistry
MH  - Chromatography, High Pressure Liquid
MH  - Humans
MH  - Kinetics
MH  - Microscopy, Atomic Force
MH  - Muscular Dystrophy, Oculopharyngeal/*metabolism
MH  - Peptides/chemistry
MH  - Poly(A)-Binding Protein I/*chemistry/*physiology
MH  - Protein Structure, Tertiary
MH  - Recombinant Proteins/chemistry
MH  - Time Factors
MH  - Trinucleotide Repeat Expansion
EDAT- 2007/01/19 09:00
MHDA- 2007/03/10 09:00
CRDT- 2007/01/19 09:00
PHST- 2007/01/19 09:00 [pubmed]
PHST- 2007/03/10 09:00 [medline]
PHST- 2007/01/19 09:00 [entrez]
AID - EJB5595 [pii]
AID - 10.1111/j.1742-4658.2006.05595.x [doi]
PST - ppublish
SO  - FEBS J. 2007 Jan;274(2):346-55. doi: 10.1111/j.1742-4658.2006.05595.x.