Lecture 13: Protein Misfolding and Disease II Flashcards
How are scrapie (sheep), BSE (bovine), and CJD (humans) characterized?
transmissible spongioform encephalopathies (TSE) (prion diseases)
How can CJD be transmitted from humans to primates?
direct implantation of plaque
What are found in damaged areas of the brain after death by TSE’s?
amyloid plaques
What is the most definitive test for neurodegenerative diseases, such as TSE?
post mortem staining
although not the most definitive, what test can be used to detect neurodegenerative diseases?
PET scan
What did Prusiner do?
isolate protein which induces prion diseases
discover/isolate PrPc and PrPsc
no nucleic acid
What did electron micrographs reveal about TSE?
has islet amyloid polypeptide - organized fibrils
How is the infectivity of the TSE infective particle Not reduced? How is reduced?
NOT: conventional methods for sterilization (heat, irradiation)
Reduced: proteins denaturants (NaOH, SDS, guanidine hydrochloride)
How are the genetics of fatal familial insomnia and CJD similar?
common primary site mutation
either Met or Val at secondary site
How is PrP characterized? Where is it expressed?
glycoprotein
brain, other organs
There are two covalently identical forms of PrP. What does this mean?
exact same peptide different conformations (fold differently)
How do PrPsc’s bind to one another? What is this called?
beta sheet
growth
When PrPc is converted to PrPsc, adnd several PrPsc molecules bind to one another, what is this called?
nucleation
List 4 characterizing features of PrPc
- non-pathogenic
- soluble
- protease sensitive
- 40% alpha helix, little beta sheet
List 4 characterizing features of PrPsc
- pathogenic
- insoluble
- protease insensitive
- 30% alpha helix, 45% beta sheet