protein folding presentation
DESCRIPTION
A lecture on Protein folding that explains the role of primary, secondary and tertiary structure of proteins. It also explains some post transnational modifications that proteins undergo on their path to maturationTRANSCRIPT
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What factors influence protein function? What is denaturation ? What is inactivation?
What forces underlie the folding process? What are the consequences of protein misfolding?
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Factors influencing protein activity Denaturation Vs inactivation
Denaturation ……Random coil: no specific shape.
Is it reversible?
Inactivation/activation form of regulation may be reversible or irreversible.
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In/activation Covalent modification
Reversible: phosphorylation/dephosphorylation
Irreversible: Proteolysis
Acylation ex: Myristoylation, palmitoylation
Allosteric modulators positive and negative
Conformational: monomer - polymer
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Denaturing Agents
Harsh mechanical treatment/handling
Heat
How does changes in temperature affect protein function?
Heat Kinetic energy
(Taq-polymerase), freezing and thawing
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Acid-base: Charge disruption
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Alcohol
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Denaturating agents Salt concentration +NH4 > k> + Na + > Li + > Mg++ > Ca++ precipitating
Urea solubilizing Guanidium
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Disulfide reduction Mercaptoethanol, Dithiothreitol…
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Detergents:
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SDS:
Sodium dodecyl sulfate, Sodium lauryl sulfate
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Other denaturing agents Heavy metals: Pb, Hg, Cd, Ag
UV ionizing radiation
Will a denatured protein re-nature into its native conformation?
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Anfinsen Experiment
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Protein folding IS IT RANDOM?
What forces direct the folding?
∆ G = ∆ H - T ∆ S
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Folding Pathways
Not random.
The folding process is rapid
Determined by the primary sequence and surrounding environment,
Requires sometimes accessory proteins.
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Accessory Proteins
Prolyl cis –trans isomerase
Protein Disulfide Isomerase…… PDI
Chaperons
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Prolyl cis-trans isomerase
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Protein disulfide Isomerase (PDI)
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Chaperons Heat shock proteins
HSP 70 ……. Blocks aggregation
HSP60 …… Provides isolation chamber
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Protein Fate
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Protein Misfolding
Protein Conformational Diseases
in 2ry and/or 3ry structure of functional protein
Loss of function or gain of toxic activity
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PFD
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PrPC/PrPSc
1. PrPSc bind to PrPC
2. Leads to “Flipping”
of PrPC into a beta-
sheet conformation
(PrPSc)
3. PrPSc can Polymerize
4. Lead to the formation
of fibrils and plaques
5. Deposit in brain
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Sickle hemoglobin