PRION THE INFECTIOUS PROTEIN

1. PRIONS
THE
INFECTIOUS
PROTEINS
JUDAH F.KAPU
TEACHER IN CHARGE :Prof. NK
CHRUNGOOMSC IInd SEM

3. PRION
•Stanley B. Prusiner (1982) coined the term Proin from
Proteinaceous infective particle
and changed to prion to sound it rhythmic.
 Prion are aggregates of misfolded prion protein.
 Infectious agent
Mad cow(BSE)KURUScrapieCJD

4. What exactly is a PRION?
Chromosome 20 (human)
PrPc=Prion Protein cellular form
PrPRES=Prion Protein Resistance Form

5. PrPc VS PrPsc
α- helices
Β-Sheet
43% 30%
03% 43%
Dominant Quaternary Monomer Aggregate
Digested by Protinease K Yes NO

6. Holger Wille et Jesús R. Requena
STRUCTURE OF PRION (PRPres or PRPsc)

7. C. Weissmann, M. Enari , P.-C. Klo¨hn, D. Rossi , and E. Flechsig
Models for the conformational conversion of PrPc to PrPsc

8. PrPC
PrPSC
PrPC
Mechanism of plaque formation

9. PrPsc fibrils

10. Plaque

11. How does a person or animal get prion diesease?
1) Spontaneous Misfolding of PrP
Eg.Sporadic form of CJD,Gerstmann Straussler sheinker
syndrome)
•Eugene Sulkowski; Spontaneous conversion of PrP c to PrP s°; Volume 307,
number 2, 129-130 FEBS 1 1292© 1992 Federation of European Biochemical
Societies
2) Having version of PrP gene that encourage
misfolding
Eg.Fatal famillial insomnia
3)Direct contact with PrPsc
Eg.BSE,vCJD,KURU

12. Kuru is a neurodegenerative disorder
that surfaced among the South Fore of
New Guinea.
A map of kuru prevalence in early fifties.
(Courtesy of Dr. D.C. Gajdusek,
Paris, France.)
KURU
Work pioneered by Gadjusek(1996)
Lindenbaum(1979) , Zigas
Victims of kuru were mostly women
and children.
Symptoms include memory
impairment, inappropriate laughter,
Unsteadiness in gait etc

13. KURU cont….
Dr. D. Carleton Gajdusek

14. BOVINE SPONGIFORM
ENCEPHALOPATHY(BSE)
 Commonly known as Mad cow
disease
 BSE is a progressive, fatal disease
of the nervous system of cattle,
 BSE in cattle was first observed in
the United Kingdom (UK) in 1986
(Wells et al., 1987)
 Currently no treatment or vaccine
for the disease.
 It is neurological disease involving
pronounced changes in mental
state, abnormalities of posture and
movement and of sensation.

16. Some of the great things about PRIONS
• Prion form a mechanism for the inheritance of
Protein based trait
• They causes dozen of new trait
• They allow the organism(Yeast) to survive the
fluctuating environment
• Prion form the ultimate example of Lamarckian
Evolution

17. Odd genetic behavior
Cox,Tuite,Ter-Avenesyan,Liebman,Sherman et al

18. Hsp104 breaks fibreto form SEED

20. Once [GAR+] appears It is very stable

21. [GAR+] is induced by a chemical factor in the environment

22. Jean-Baptiste Lamarck
There are
mechanisms by
which changes in the
environment induce
new traits that can
be passed on to
progeny in a stable
heritable form.