Protein folding diseases

L.Revathi
14MG12

What is protein folding?

Proteins are the basis of how biology gets
things done.
In order to carry out their function (e.g. as
enzymes or antibodies), they must take on a
particular shape Protein folding.
A small error in the folding process results in a
misfolded structure which results in many
diseases.

What happens if proteins dont fold

correctly?

(A) Native polypeptide chain composed of mainly -helical secondary

structure.
(B) Misfolding causes conversion of -helical structure to -pleated sheets and
(C) final misfolded structure of polypeptide chain contains mostly -pleated
sheets.

Cellular consequences of protein aggregation

Loss-of-function pathogenesis: if misfolded
proteins are prematurely degraded by PQC system
protein deficiency disease
Gain-of-function pathogenesis: if misfolded
proteins are not eliminated but accumulated instead
disease pathology
toxicity

Protein dimerization & oligomerization.

Misfolded monomers forming aggregate

through intermolecular hydrogen bonding
interaction leading to -sheet formation.

Alzheimers disease
The extracellular deposition of beta amyloid
plaques and neurofibrillary tangles (NFT) in
the brain.

Prion diseases

Transmissable spongiform encephalopathies

(TSEs)
CreutzfeldtJakob disease
Bovine spongiform
encephalopathy (mad
cow disease)

Protein misfolding diseases

Fate of misfolded proteins

The role of chaperones in rescuing protein

conformational defects

 Mutational effect in human proteins

are corrected by molecular, chemical
and pharmacological chaperones.

Conclusion
Whatever the reason for a protein not
achieving its functional form, it is the
conformational defect that leads to disease.
Chaperones play a critical role in controlling
protein misfolding and thus reducing the threat
of associated protein misfolding diseases.

Thank you