title: Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent.
abstract: Nucleic acid can catalyze the conversion of α-helical cellular prion protein to β-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered α-helical structure is considered to be a necessary step for the structural conversion to its β-sheet rich isoform, we have studied the unfolding of the α-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein.
authors.affiliation: Infectiologie Animale et Santé Publique, Institut National de la Recherche Agronomique, 37380, Nouzilly, France.
authors.forename: Alakesh
authors.initials: A
authors.lastname: Bera
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Nandi
mesh_terms: D000818:Animals; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009696:Nucleic Acids / Q000737:chemistry* / Q000494:pharmacology; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation / Q000187:drug effects; D058767:Protein Unfolding / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry; D013696:Temperature
chemical_list: D009696:Nucleic Acids; D011328:Prions; D011994:Recombinant Proteins
keywords: PloyA; denaturation temperature (Tm); nucleic acids; pH 5; prion protein