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Lecture_09-Protein_Misfolding - SOME PROTEINS NEED HELP...

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PROTEIN MIS-FOLDING What happens if folding goes wrong? 1 SOME PROTEINS NEED HELP FOLDING not all proteins fold correctly spontaneously folding for some proteins is facilitated by chaperones proteins that interact with partially folded or improperly folded polypeptides 2 cap heptamer heptamer The GroEL-ES System Protein Disulfde Isomerase (PDI) Peptide prolyl cis-trans isomerase (PPIase) 3 FOLDING DISEASES Mis-folding can cause disease Type 2 diabetes Alzheimer’s disease Huntington’s disease Parkinson’s disease some caused by extracellular deposition of normally soluble proteins aggregates called amyloid diseases that stem from amyloid formation are collectively referred to as amyloidoses 4
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AMYLOIDOGENIC PROTEINS proteins that generate amyloid often unrelated and have different native structures widely different 3° structure a common feature a higher concentration of aromatic amino acid residues in a core region of beta sheet 5 AMYLOIDOGENIC PROTEINS amyloid forms are similar 7-10 nm diameter of amyloid Fbrils mainly β -sheet strands are perpendicular to the axis of the Fbril 6 ±ORMATION O± THE ±IBRIL 1. Protein misfolds somehow and β -core forms or reforms 2. Hydrophobic cores of misfolded proteins aggregate 3. Aggregation continues to form the beginning of the Fbril 7 MODEL O± AMYLOID ±IBRILS Axial Direction strand direction http://www.endocytosis.org/ImaginingTheBrain/NeuroArt2007/ Neurodegeneration.html 8
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Lecture_09-Protein_Misfolding - SOME PROTEINS NEED HELP...

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