Protein folding and aggregation
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Transcript of Protein folding and aggregation
Faizan Abul Qais
2013MBM02
Dept. of Ag. Microbiology
PROTEIN FOLDING
AND
AGGREGATION
Protein structure
Protein folding
Models of protein folding
Protein Aggregation
Manifestations of protein aggregation
Affecting factors
Diseases associated with protein aggregation
Conclusion
References
Content:
Protein Structures Primary structure Secondary structure
Protein Structures Tertiary structure Quaternary structure
Protein Folding
Process by which a protein assumes its functional
conformation.
Factors that guide in proper protein folding are:
(i). Amino acid sequence
(ii). Cellular environment
The folded 3-D structure of most proteins represent a
compromise between thermodynamic stability and
the conformational flexibility required for function.
A substantial fraction of proteins in eukaryotic cells(∼30%) are classified as intrinsically unstructured, such
proteins are prone to aggregation.
Models of protein folding
Protein-energy funnel
Energy landscape
Protein aggregation
It is a phenomenon wherein the protein loses itsnative structure and adopts a non-nativeconformation.
Despite the many processes that assist inprotein folding, misfolding does occur.
Failure produces inactive proteins that areusually toxic in nature.
Common diseases associated with proteinmisfolding are Alzheimer’s, Parkinson’s priondiseases etc.
Overview of protein aggregation
Translation Rate and protein folding
Protein aggregation results in
Amyloid fibrils.
Inclusion bodies.
Soluble oligomers.
Inclusion bodies Dense particles of
aggregated proteins. These are porous and
hydrated. Exhibit amorphous as well
as partly ordered structure. Structural heterogeneity is
observed. Proteins prone to form
inclusion bodies are exposed hydrophobic patches.
Amyloid fibrils
Generic property of all proteins.
Associated with a number of fatal
diseases.
Fibrils take the form of a β-sheet, hence
the name β-amyloid.
Accumulate in variety of organs.
Once formed, they are nearly
indestructible and controlling their
growth is impossible.
Affecting factors
Sequence based
Hydrophobicity
Net charge
Secondary structural propensities
Environment based
Protein concentration
pH
Temperature
Salt conc.
Some associated diseasesDiseases Protein
involved
Modification Manifestation
Alzheimer’s disease
Amyloid-β Aberrant processing Extracellular amyloid
plaques
Parkinson’sdisease
α-Synuclein Aberrant ubiquination Cytoplasmic
inclusion bodies
Sickle cell anemia Hemoglobin Substitution of Glu to
Val
Sickle shaped RBC
Huntington’sdisease
Huntingtin Poly-glutamine
(CAG) mediated
protein aggregation
Intranuclear inclusion
bodies
Conclusion
Protein aggregation results in the formation ofamyloid fibrils and inclusion bodies which areassociated with many neurodegenerativedisorders and prions related diseases.
Understanding the structure and mechanisticaspects might provide a solution to manypossible therapies.
A key one might be able to find a smallmolecule (drug) targeting for the disruption ofmisfolded one.
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http://en.wikipedia.org
“A journey from amino acid to protein” by Saad Taiyab
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