PRIONSAn Exception To Central

DogmaPrepared & Presented by

Tareq Hasan

ID : 141 1989 070Submitted to

Prof. M. Anwar Hossain

A Scientific Seminar Presentation on

Course

Advanced Biochemistry & Molecular Biology (BBT 608)

MSc in Biotechnology

Department of Biochemistry & Microbiology

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WHAT is “CENTRAL DOGMA”• In 1958 and It was re-stated in Nature journal in 1970

• The word “DOGMA” = Something that is “UNCHANGABLE”

• It deals with the detailed, sequential & residue-by-residue transfer of genetic information, i.e. –

DNA mRNA PROTEIN• And, once getting into the proteins, GENETIC INFORMATION CANNOT BE TRANSFERRED BACK FROM PROTEIN TO EITHER PROTEIN Or nucleic acid.

Dr. Francis Crick giving a lecture on Central

Dogma at Cambridge University at 1958

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Prions

Prions are infectious particles.

They lack nucleic acid & is made only of protein.

Prions are aberrantly folded and convert normal proteins into their configuration.

So, prions are misfolded Proteinaceous Infectious Particles.

Diseases caused by Prions are called “Transmissible Spongiform Encephalopathy”.

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Discovery & Naming of Prions

In 1982, He isolated‘The Infectious Prion Proteins (PrPSC) involved in Mad Cow Disease’.

He won Noble Prize in 1997

Dr.

Stanl

y B.

Prusine

r

The term was first coined as –

Proin =

Pro

teinaceous

In

fectiousParti

cles

Prion

Dr. S. B. Prusinerrearranged the term forsounding more rhythmic

Type of Prions & Their Differences

C = Cellular

Encoded by PrP Gene

Globular Protein

Soluble in H2O

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Sc = Scrapie

Encoded by PRNP Gene, a mutated PrP Gene

Fibrous Protein

Insoluble in H2O

PrPC PrPSC

Structures of Different Prions

PrPC

PrPSC

1. Globular protein2. Composed of α –

helix.3. Consist of

Asparagine at position 129

4. Protease Sensitive5. Not infectious

1. Fibrous protein2. Composed of β –

sheets.3. Consist of Valine at

position 1294. Protease Resistant5. Infectious

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Functions of PrPC

Copper Ion Binding

Protein Binding

Microtubule Binding

Tubulin Binding

Identical Protein Binding

Atp-dependent Protein Binding

Chaperone Binding

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Pathogenesis of Infections Prion PrPSC

IntestineIngestion of Prions

Peripheral Nervous System

Lymphatic System1. Lymph Nodes2. Spleen

Central Nervous System

1. Spinal Cord2. Brain

Peripheral Nervous System

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Replication of Infectious Prion, PrPSC, The Rotten Apple

+

PrPc

PrPSc PrPSC has a template domainto which the PrPc can bind

and rearrange & makes - amylofibril

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Replication of Infectious Prion, PrPSC, The Rotten Apple

Accumulation of - amyloid fibril in the neurons results in their necrosis

As a result, the part of the destroyed brain cells looks like sponge.

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Prion Diseases:Transmissible Spongiform

Encephalopathies

Depending on the regions of the brain where the - amyloid proteins are accumulated –Prion diseases are as in folowing figure.

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Prion Diseases:Transmissible Spongiform

EncephalopathiesDisease Description

Infectious Diseases

Kuru• Human disease• Begins with a loss of coordination & dementia

Scrapie

• Disease of sheep and pigs• Intense itching in which animals scrape

themselves into the trees Followed by neurodegeneration

Mad cow disease (BSE)• Begins with changes in posture and temperament• Followed by loss of coordination and

neurodegeneration

Human Inherited Diseases

Creutzfeldt-Jakob disease

• Characterized by loss of coordination and dementia

Gerstmann-Straussler-Scheinker disease

• Characterized by loss of coordination and dementia

Familial fatal insomnia• Begins w/ sleeping and ANS disturbances• Followed by insomnia and dementia

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THANK YOU

THE END