11.5 Flashcards
What is the brain pathology in transmissible spongiform encephalopathies
Spongiosis: spongey appearance with neuronal loss
Three forms of TSEs
Genetic
Infectious
Sporadic
What are some TSEs (4)
Creutzveldt-Jakob Disease
Fatal familial insomnia
Gerstmann-traussler-Scheinker Disease
Kuru
How did bovine spongiform encephalopathy become an issue
Transmission from sheep to cows by infectious agent in meat
What was the infectious material in TSEs
Protein aggregate with B-sheet amyloid nature
How can scrapie infectivity be reduced
Procedures that hydrolyse or modify proteins
What is the prion protein in normal animals
Membrane anchored glycoprotein
What is the only difference identifiable between normal PrP and PrPSc
Normal soluble prion protein is readily digestable by Proteinase K but infectious, aggregated PrPSc is resistant
Conversion of PrP to PrPSc
1) Spontaneous conversion through contact
2) Inoculation with infectious . material
What are some characteristics of aggregated form (2)
Cross-B core
Short peptide from N-terminal critical
How are phenotypes of prion diseases passed from infected animals
Current hypothesis is there are distinct forms of prion aggregate which recruit normal cellular form into growing aggregate
What makes some individuals more suscepitble to vCJD
Individuals who have SNP, MM or VV at codon 129 in PrP
What are some functional amyloid fibrils (3)Wher
1) Yeast prions
2) Filamentous fungi
3) Mammalion amyloid - Pmel
What was the change in phenotype observed in different prion strains
Prion strains form white colonies
Prion deficient appear red
How have prions been ‘cured’ in yeast cultures
Where aggregated prion material is converted back to soluble form by growing cell on plates containing protein denaturants such as guanidine hydrochloride
What does prion inheritance in yeast depend on
Whether aggregated material is passed when yeast divide
What is Sup35 in yeast
Component of translation termination machinery
What does the aggregated state of Sup35 result in
Reduced fidelity with which ribosomes terminate translation at stop codons
Prion propagates and can capture newly made Sup35 to perpetuate loss of function
What is an occasional benefit of non-functional Sup35
Diverse phenotypic effects, allows yeast to try phenotypes
Prion formation and loss was affected by (2)
Stress (which upregulates_
Action of chaperone
What are some functions of amyloid in filamentous fungi (4)
1) Reducing surface tension at the air:water interface
2) Coating spores for aerial dispersal
3) Mediating attachment to surfaces
4) Interaction with host
What is the function of the RodA layer re: immune system
Masks recognition of cell wall from host immune system
Where are functional amyloids found in mammalian cells
Organelles within melanocytes
What is the role of Pmel17 fibrils in melanocytes (2)
1) Template melanin synthesis along fibrils
2) Prevent toxic melanin precursors leaking out and doing damage
