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Is there a Way towards the Thermodynamics of Fibril Formation?
Author(s) -
Buttstedt Anja,
Sackewitz Mirko,
Schmid Franz Xaver,
Schwarz Elisabeth
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.851.1
Subject(s) - fibril , alanine , biophysics , cold shock domain , chemistry , bacillus subtilis , sequence (biology) , protein domain , protein structure , amyloid fibril , crystallography , fusion protein , function (biology) , biochemistry , amino acid , microbiology and biotechnology , biology , amyloid β , recombinant dna , rna , medicine , genetics , disease , pathology , gene , bacteria
The effect of the polypeptide environment on poly‐alanine induced fibril formation was investigated with amyloidogenic fragments from PAPBN1, a nuclear protein controlling poly‐adenylation. Mutation‐caused extensions of the natural ten alanine sequence up to 17 alanines result in fibril formation of PABPN1 and the development of the disease oculopharyngeal muscular dystrophy. We explored the influence of fibril formation on the structure and function of a protein domain linked to the fibril‐forming part of PABPN1. A well‐characterized, stably folded one‐domain protein, cold shock protein B from Bacillus subtilis was fused either to the C‐terminus of the entire N‐terminal domain of PABPN1 or directly to a peptide consisting of ten alanine residues. The fusion protein of the N‐terminal domain and CspB formed fibrils in which the structure and activity of CspB were retained. In the fibrils formed by fusions in which the poly‐alanine sequence was directly linked to CspB, CspB was unfolded. These results indicate that the folded conformation and the function of a protein domain can be maintained in amyloid‐like fibrils and that the distance between this domain and the fibril plays an important role.