Prions: Native vs. Model system

Donovan Duggan

Eukaryotes

• Humans

• Cows

• Sheep

• Hamsters

• Mice

• Cervids

Prokaryotes

E.coli

Eukaryote

Central Dogma

Protein Localization

• Transport to the endoplasmic reticulum H2N-Met-Met-Ser-Phe-Val-Ser-Leu- Leu-Leu-Val-Gly-Ile-Leu-Phe- Trp-Ala-Thr-Glu-Ala-Glu-Gln- Leu-Thr-Lys-Cys-Glu-Val-Phe- Gln-

• Retention to the endoplasmic reticulum -Lys-Asp-Glu-Leu-COOH

Eukaryote

ER Lumen

Prion protein processing in the ER

Prion protein trafficking and the development of neurodegeneration

Ramanujan S. Hegde and Neena S. Rane

Prokaryote

Same Central Dogma

Prokaryote

Inclusion Bodies

Things to Mimic

• ER conditions – Primary folding…

• Cytoplasmic conditions– Aggregation and amyloid formation– Intermediates

Peptide possibilities

Thanks

• David Wishart

• All of you for listening