Probing the Residual Structure in Avian Prion Hexarepeats by CD, NMR and MD Techniques
AbstractMany proteins perform essential biological functions by means of regions that lacking specific organized structure exist as an ensemble of interconverting transient conformers. The characterization of such regions, including the description of their structural propensities, number of conformations and relative populations can provide useful insights. Prion diseases result from the conversion of a normal glycoprotein into a misfolded pathogenic isoform. The structures of mammal and chicken prion proteins show a similar fold with a globular domain and a flexible N-terminal portion that contains different repeated regions: octarepeats (PHGGGWGQ) in mammals and hexarepeats (PHNPGY) in chickens. The higher number of prolines in the hexarepeat region suggests that this region may retain a significant amount of residual secondary structure. Here, we report the CD, NMR and MD characterization of a peptide (2-HexaPY) composed of two hexarepeats. We combine experimental NMR data and MD to investigate at atomic level its ensemble-averaged structural properties, demonstrating how each residue of both repeats has a different quantified PPII propensity that shows a periodicity along the sequence. This feature explains the absence of cooperativity to stabilize a PPII conformation. Nonetheless, such residual structure can play a role in nucleating local structural transitions as well as modulating intra-molecular or inter-molecular interactions.
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Russo, L.; Raiola, L.; Campitiello, M.A.; Magrì, A.; Fattorusso, R.; Malgieri, G.; Pappalardo, G.; La Mendola, D.; Isernia, C. Probing the Residual Structure in Avian Prion Hexarepeats by CD, NMR and MD Techniques. Molecules 2013, 18, 11467-11484.
Russo L, Raiola L, Campitiello MA, Magrì A, Fattorusso R, Malgieri G, Pappalardo G, La Mendola D, Isernia C. Probing the Residual Structure in Avian Prion Hexarepeats by CD, NMR and MD Techniques. Molecules. 2013; 18(9):11467-11484.Chicago/Turabian Style
Russo, Luigi; Raiola, Luca; Campitiello, Maria A.; Magrì, Antonio; Fattorusso, Roberto; Malgieri, Gaetano; Pappalardo, Giuseppe; La Mendola, Diego; Isernia, Carla. 2013. "Probing the Residual Structure in Avian Prion Hexarepeats by CD, NMR and MD Techniques." Molecules 18, no. 9: 11467-11484.