Does tetracycline bind helix 2 of prion? An integrated spectroscopical and computational study of the interaction between the antibiotic and α helix 2 human prion protein fragments - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proteins: Structure, Function and Genetics Année : 2007

Does tetracycline bind helix 2 of prion? An integrated spectroscopical and computational study of the interaction between the antibiotic and α helix 2 human prion protein fragments

E. Langella
  • Fonction : Auteur
P. Palladino
  • Fonction : Auteur
D. Marasco
  • Fonction : Auteur
B. Tizzano
  • Fonction : Auteur
M. Saviano
  • Fonction : Auteur
C. Pedone
  • Fonction : Auteur
R. Improta
  • Fonction : Auteur
M. Ruvo
  • Fonction : Auteur

Résumé

We demonstrate here that tetracycline (TC) can strongly interact (K D′ = 189 ± 7 nM) with model peptides derived from the C-terminal globular domain of the prion protein, hPrP [173-195], and that interaction concerns residues within the C-terminal half of the helix 2, a short region previously indicated as endowed with ambivalent conformational behavior and implicated in PrP conversion to the β-sheet-rich, infective scrapie variant. Data have been confirmed by binding studies with the N-terminal truncated 180-195 variant that displays a dissociation constant of 483 ± 30 nM. Remarkably, TC does not influence the structure of the N-terminally fluoresceinated peptides that both show α-helical conformations. Docking calculations and molecular dynamics simulations suggest a direct, strong interaction of the antibiotic with exposed side chain functional groups of threonines 190-193 on the solvent-exposed surface of helix 2. © 2006 Wiley-Liss, Inc.

Domaines

Chimie

Dates et versions

hal-01563752 , version 1 (18-07-2017)

Identifiants

Citer

Luisa Ronga, E. Langella, P. Palladino, D. Marasco, B. Tizzano, et al.. Does tetracycline bind helix 2 of prion? An integrated spectroscopical and computational study of the interaction between the antibiotic and α helix 2 human prion protein fragments. Proteins: Structure, Function and Genetics, 2007, 66 (3), pp.707-715. ⟨10.1002/prot.21204⟩. ⟨hal-01563752⟩
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