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Protein folding diseases

L.Revathi

14MG12

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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.

• ! small error in the folding process results in a

misfolded structure which results in many

  diseases.

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What happens if proteins don"t fold

correctly?

(!) #ati$e polypeptide chain composed of mainly %&helical secondarystructure.

(') isfolding causes con$ersion of %&helical structure to &pleated sheets and

(*) final misfolded structure of polypeptide chain contains mostly &pleated

sheets.

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*ellular conse+uences of protein aggregation

•  Loss-of-function pathogenesis if misfolded

 proteins are prematurely degraded by P-* system

 protein deficiency disease

•  Gain-of-function pathogenesis if misfolded

 proteins are not eliminated but accumulated instead

 disease pathology

 toicity

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Protein dimerization / oligomerization.

• isfolded monomers forming aggregate

through intermolecular hydrogen bonding

interaction leading to &sheet formation.

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!lzheimer"s disease

• 0he etracellular deposition of beta amyloid

 pla+ues and neurofibrillary tangles (#10) in

the brain.

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Prion diseases

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0ransmissable spongiform encephalopathies

(023s)

• *reutzfeldt4akob disease

• 'o$ine spongiform

encephalopathy (mad  cow disease)

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Protein misfolding diseases

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1ate of misfolded proteins

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0he role of chaperones in rescuing protein

conformational defects

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• Mutational efect in human proteins

are corrected by molecular, chemicaland pharmacological chaperones.

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0hank you