title: The human prion protein alpha2 helix: a thermodynamic study of its conformational preferences.
abstract: We have synthesized both free and terminally-blocked peptide corresponding to the second helical region of the globular domain of normal human prion protein, which has recently gained the attention of structural biologists because of a possible role in the nucleation process and fibrillization of prion protein. The profile of the circular dichroism spectrum of the free peptide was that typical of alpha-helix, but was converted to that of beta-structure in about 16 h. Instead, below 2.1 x 10(-5) M, the spectrum of the blocked peptide exhibited a single band centered at 200 nm, unequivocally associated to random conformations, which did not evolve even after 24 h. Conformational preferences of this last peptide have been investigated as a function of temperature, using trifluoroethanol or low-concentration sodium dodecyl sulfate as alpha- or beta-structure inducers, respectively. Extrapolation of free energy data to zero concentration of structuring agent highlighted that the peptide prefers alpha-helical to beta-type organization, in spite of results from prediction algorithms. However, the free energy difference between the two forms, as obtained by a thermodynamic cycle, is subtle (roughly 5-8 kJ mol(-1) at any temperature from 280 K to 350 K), suggesting conformational ambivalence. This result supports the view that, in the prion protein, the structural behavior of the peptide is governed by the cellular microenvironment.
authors.affiliation: Dipartimento di Chimica Biologica, Università Federico II di Napoli, Napoli, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tizzano
authors.forename: Pasquale
authors.initials: P
authors.lastname: Palladino
authors.forename: Antonia
authors.initials: A
authors.lastname: De Capua
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.forename: Filomena
authors.initials: F
authors.lastname: Rossi
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ragone
authors.forename: Menotti
authors.initials: M
authors.lastname: Ruvo
mesh_terms: D006801:Humans; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate; D013816:Thermodynamics
chemical_list: D011328:Prions; D012967:Sodium Dodecyl Sulfate