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Putative aggregation initiation sites in prion protein
Author(s) -
Ziegler Jan,
Viehrig Christine,
Geimer Stefan,
Rösch Paul,
Schwarzinger Stephan
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.03.002
Subject(s) - sequence (biology) , prion protein , protein aggregation , peptide , chemistry , biophysics , protein folding , peptide sequence , prion proteins , protein structure , biochemistry , microbiology and biotechnology , biology , gene , medicine , disease , pathology
Misfolded prion protein, PrP Sc , is believed to be the pathogenic agens in transmissible spongiform encephalopathies. Little is known about the autocatalytic misfolding process. Looking at the intrinsic properties of short sequence stretches, such as conformational flexibility and the tendency to populate extended conformers, we have examined the aggregation behaviour of various peptides within the region 106–157 of the sequence of human prion protein. We observed fast aggregation for the peptide containing residues I138‐I‐H‐F141. This sequence, which is presented at the surface of cellular prion protein, PrP C , in an almost β‐sheet‐like conformation, is therefore an ideal anchor‐point for initial intermolecular contacts leading to oligomerization. We further report that the aggregation propensity of the neurotoxic peptide 106–126 appears to be centred in its termini and not in the central, alanine‐rich sequence (A113‐G‐AAAA‐G‐A120).