Determination of solution conformations of PrP106-126, a neurotoxic fragment of prion protein, by 1H NMR and restrained molecular dynamics

Enzio Ragg, Fabrizio Tagliavini, Paolo Malesani, Luca Monticelli, Orso Bugiani, Gianluigi Forloni, Mario Salmona

Research output: Contribution to journalArticlepeer-review


Experimental two-dimensional 1H NMR data have been obtained for PrP106- 128 under the following solvent conditions: deionized water/2,2,2- trifluoroethanol 50 : 50 (v/v) and dimethylsulfoxide. These data were analyzed by restrained molecular mechanics calculations to determine how changes in solvation affect the conformation of the peptide. In deoinized water at pH 3.5, the peptide adopted a helical conformation in the hydrophobic region spanning residues Met112-Leu125, with the most populated helical region corresponding to the Ala115-Ala119 segment (≃ 10%). In trifluoroethanol/H2O, the α-helix increased in population especially in the Gly119-Val122 tract (≃ 25%). The conformation of this region was found to be remarkably sensitive to pH, as the Ala120-Gly124 tract shifted to an extended conformation at pH 7. In dimethylsulfoxide, the hydrophobic cluster adopted a prevalently extended conformation. For all tested solvents the region spanning residues Asn108-Met112 was present in a 'turn-like' conformation and included His111, situated just before the starting point of the α-helix. Rather than by conformational changes, the effect of His111 is exerted by changes in its hydrophobicity, triggering aggregation. The amphiphilic properties and the pH-dependent ionizable side-chain of His111 may thus be important for the modulation of the conformational mobility and heterogeneity of PrP106-126.

Original languageEnglish
Pages (from-to)1192-1201
Number of pages10
JournalEuropean Journal of Biochemistry
Issue number3
Publication statusPublished - Dec 15 1999


  • H NMR
  • Conformation
  • Prion protein
  • PrP106-126

ASJC Scopus subject areas

  • Biochemistry


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