FEBS Letters
Volume 580, Issue 8 , Pages 2033-2040, 3 April 2006

Putative aggregation initiation sites in prion protein

Edited by Jesus Avila

  • Jan Ziegler

      Affiliations

    • Lehrstuhl Biopolymere, University Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany
    • These authors contributed equally to this work.
    • ,
  • Christine Viehrig

      Affiliations

    • Lehrstuhl Biopolymere, University Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany
    • These authors contributed equally to this work.
    • ,
  • Stefan Geimer

      Affiliations

    • Department of Biology/Electron Microscopy, University Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany
    • ,
  • Paul Rösch

      Affiliations

    • Lehrstuhl Biopolymere, University Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany
    • ,
  • Stephan Schwarzinger

      Affiliations

    • Lehrstuhl Biopolymere, University Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany
    • Corresponding Author InformationCorresponding author. Fax: + 49 921 553544.

Received 16 December 2005; received in revised form 22 February 2006; accepted 1 March 2006. published online 10 March 2006.

Abstract 

Misfolded prion protein, PrPSc, 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, PrPC, 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).

Abbreviations: PrP, prion protein, TSE, transmissible spongiforme encephalopathies, CJD, Creutzfeldt-Jakob disease, FFI, fatal familial insomnia, GSS, Gerstmann–Sträussler–Scheinker syndrome, EM, electron microscopy, CR, Congo Red, PPII, poly-proline II

Keywords: Prion protein, TSE, BSE, Aggregation initiation, Aggregation propensity, Poly-proline II

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PII: S0014-5793(06)00293-6

doi:10.1016/j.febslet.2006.03.002

FEBS Letters
Volume 580, Issue 8 , Pages 2033-2040, 3 April 2006

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