The Human Prion Protein Alpha2 Helix: A Thermodynamic Study Of Its Conformational Preferences(764 views) Tizzano B, Palladino P, De Capua A, Marasco D, Rossi F, Benedetti E, Pedone C, Ragone R, Ruvo M
Dipartimento di Chimica Biologica, Univ. Federico II di Napoli, Napoli, Italy
Ist. Biostrutture Bioimmagini C.N.R., Napoli, Italy
CIRPeB, Napoli, Italy
Dipto. di Biochimica e Biofisica, Seconda Università di Napoli, Napoli, Italy
Ist. di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 6, 80134 Napoli, Italy
References: Not available.
The Human Prion Protein Alpha2 Helix: A Thermodynamic Study Of Its Conformational Preferences
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. (C) 2005 Wiley-Liss, Inc
The Human Prion Protein Alpha2 Helix: A Thermodynamic Study Of Its Conformational Preferences