title: Effect of the electrostatic surface potential on the oligomerization of full-length human recombinant prion protein at single-molecule level.
abstract: The electrostatic surface potential (ESP) of prion oligomers has critical influences on the aggregating processes of the prion molecules. The atomic force microscopy (AFM) and structural simulation were combined to investigate the molecular basis of the full-length human recombinant prion oligomerization on mica surfaces. The high resolution non-intrusive AFM images showed that the prion oligomers formed different patterns on mica surfaces at different buffer pH values. The basic binding units for the large oligomers were determined to be prion momoners (Ms), dimers (Ds), and trimers (Ts). The forming of the D and T units happened through the binding of hydrophobic β-sheets of the M units. In contrast, the α-helices of these M, D, and T units were the binding areas for the formation of large oligomers. At pH 4.5, the binding units M, D, and T showed clear polarized ESP distributions on the surface domains, while at pH 7.0, they showed more evenly distributed ESPs. Based on the conformations of oligomers observed from AFM images, the D and T units were more abundantly on mica surface at pH 4.5 because the ESP re-distribution of M units helped to stabilize these larger oligomers. The amino acid side chains involved in the binding interfaces were stabilized by hydrogen bonds and electrostatic interactions. The detailed analysis of the charged side chains at pH 4.5 indicated that the polarized ESPs induced the aggregations among M, D, and T to form larger oligomers. Therefore, the hydrogen bonds and electrostatic interactions worked together to form the stabilized prion oligomers.
authors.affiliation: Single Molecule Study Laboratory, College of Engineering and Nanoscale Science, and Engineering Center, University of Georgia, Athens, Georgia 30605, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Single Molecule Study Laboratory, College of Engineering and Nanoscale Science, and Engineering Center, University of Georgia, Athens, Georgia 30605, USA.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Lou
authors.affiliation: College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, People's Republic of China.
authors.forename: Haiqian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Single Molecule Study Laboratory, College of Engineering and Nanoscale Science, and Engineering Center, University of Georgia, Athens, Georgia 30605, USA.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Xu
mesh_terms: D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D010446:Peptide Fragments; D011328:Prions; D011994:Recombinant Proteins; C428437:prion protein (23-231)