January 13, 2014

If protein isnt in its state thats when it becomes

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Unformatted text preview: 2004 Jul;10 Suppl:S10-7. Review. protein Misfolding -AB deposit within brain ND disorders/ hydrophobic/ How proteins aggregate and form insoluble fibrils Whats toxic? if protein isn’t in its state / thats when it becomes toxic , when it makes deposit in brain ( less toxic). Protein oxidation… Can cause proteins to agregate Representation of structural components of protein structure Protein folding and energy states protein happiesst wen they are folded. native proteins are avtive/ protein misfolding happes a lot trought its life time, increase intracellular Ph , protein can fold back to its original form • Protein folding: Only folded, native proteins are functionally active • Unfolded states: Characterized by higher degree of free energy than native states. This leads to “unstableness” of proteins when in the unfolded state. The minimum of the energy level of a protein is reached when it’s in its native/folded state. • Protein misfolding: A common and continuous phenomenon in the life of a protein • Denaturation: The process by which the native structure of protein is disrupted Protein Aggregation • If a protein is damaged it can undergo denaturation, this causes loss of the low energy state. because its high energy wants to go to low energy its forms aggregate state • The protein is then in a highly disorganized structure and tends to form aggregates to reduce the state of high energy. i.e. to stabilize Summary of protein misfolding diseases Factors that might influence protein denaturation and misfolding • Mutations protein are in monomers , one AA chain ,lot more chance to form aggregate then if you only have one AA around • Glucose levels • Oxidation • Changes in physiological pH • Binding to ions • Levels/concentrations of monomers: if low the protein tends not to aggregate, if high the protein tends to form aggregates Schematic representation of protein misfolding Something will cause it to unfold, it can form fibrils, photo fibrils then amyloid plaques, all intermediates are toxic to cell.intermediates are more toxic then AP themselves • Pathways to...
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