Narayanan, Sunilkumar Puthenpurackal and Nair, Divya Gopalakrishnan and Schaal, Daniel and de Aguiar, Marisa Barbosa and Wenzel, Sabine and Kremer, Werner and Schwarzinger, Stephan and Kalbitzer, Hans Robert (2016) Structural transitions in full-length human prion protein detected by xenon as probe and spin labeling of the N-terminal domain. SCIENTIFIC REPORTS, 6: 28419. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Fatal neurodegenerative disorders termed transmissible spongiform encephalopathies (TSEs) are associated with the accumulation of fibrils of misfolded prion protein PrP. The noble gas xenon accommodates into four transiently enlarged hydrophobic cavities located in the well-folded core of human PrP(23-230) as detected by [H-1, N-15]-HSQC spectroscopy. In thermal equilibrium a fifth xenon binding site is formed transiently by amino acids A120 to L125 of the presumably disordered N-terminal domain and by amino acids K185 to T193 of the well-folded domain. Xenon bound PrP was modelled by restraint molecular dynamics. The individual microscopic and macroscopic dissociation constants could be derived by fitting the data to a model including a dynamic opening and closing of the cavities. As observed earlier by high pressure NMR spectroscopy xenon binding influences also other amino acids all over the N-terminal domain including residues of the AGAAAAGA motif indicating a structural coupling between the N-terminal domain and the core domain. This is in agreement with spin labelling experiments at positions 93 or 107 that show a transient interaction between the N-terminus and the start of helix 2 and the end of helix 3 of the core domain similar to that observed earlier by Zn2+-binding to the octarepeat motif.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PRESSURE NMR-SPECTROSCOPY; CREUTZFELDT-JAKOB-DISEASE; CHEMICAL-SHIFT; BINDING-SITES; STAPHYLOCOCCUS-CARNOSUS; DISULFIDE BOND; CONVERSION; RECOMBINANT; COPPER; PRP; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2019 08:55 |
| Last Modified: | 08 Apr 2019 08:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3749 |
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