Structural characterization of recombinant PrPSc prions using biochemical and biophysical techniques
- Autores: Yaiza Bugallo Codeseira
- Directores de la Tesis: Jesús Rodríguez Requena (dir. tes.)
- Lectura: En la Universidade de Santiago de Compostela ( España ) en 2022
- Idioma: inglés
- Tribunal Calificador de la Tesis: Byron Caughey (presid.), Eduardo Dominguez Medina (secret.), Joaquín Castilla Castrillón (voc.)
- Programa de doctorado: Programa de Doctorado en Medicina Molecular por la Universidad de Santiago de Compostela
- Materias:
- Enlaces
- Tesis en acceso abierto en: MINERVA
- Resumen
Prion diseases i.e. Creutzfeldt-Jakob disease (CJD) and related disorders, are rare, fatal brain neurodegenerative ailments. Their worldwide yearly incidence is of about one case per million people, i.e., approximately 8000 new cases per year in the world. They are caused by the autopropagative misfolding of the prion protein, PrP, namely PrPSc. Despite extensive efforts, effective drugs against these disorders are still lacking, very likely due to the fact that the structure of PrPSc is still unknown.This thesis proposal aims at elucidating the structure of such prion using different biochemical and biophysical techniques. The main technique employed is solid state nuclear magnetic resonance (ssNMR) by which we analyzed for the first time recombinant BVPrPSc sample produced by the PMSA technique, along with some controls that allowed us to obtain an array of structural information. The most relevant piece of information obtained by analyzing 13CO-Phe- Het-s, a yeast prion, 13CO-Phe-PrP amyloid which is non infectious and recBVPrPSc was the secondary structure of the latter conforms to a PIRIBS (parallel-in-register-intermolecular-beta-sheets) structure contrary to our initial hypothesis that its secondary structure was that of a 4RBS (4-rung-beta-solenoid). In my thesis I present all the details of how I arrived to this conclusion along with others.
