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22 Cards in this Set
- Front
- Back
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What are the two main methods of pre-translational quality control?
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Aminoacyl- tRNA synthetase- The AARS is a key site for quality control in preventing misacylation of tRNA's by selection and editing processes.
Ribosomal proofreading - the ribosome uses a proofreading mechanism to prevent the wrong tRNA from binding to the A-site codon. |
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What is NMD?
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Nonsense mediated mRNA decay - 10 % of mRNA's have this mechanism that recognizes and degrades transcripts with a premature stop codon.
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How does the mechanism of NMD work?
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Translation termination requires an interaction of the ribosome with the poly-A binding protein. The distance between the two is crucial in recognition of the PTC. NMD works by placing an Exon Junction Complex near the sites of splicing and this is what detects premature stop codons upstream of the final exon. The mRNA is then targeted for degradation.
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Protein quality control systems are found in 3 places
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Cytoplasm
ER - contains a set of chaperones and folding enzymes that assist protein folding in conjunction with post-translational modifications Mitochondria - Have their own translation system. |
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Newly synthesized proteins sometimes fold correctly and assemble with their partner proteins without help. In most cases, they are helped by
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Molecular Chaperones
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What are the 4 functions of chaperones/cochaperones?
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-protect nascent polypeptides from misfolding, facilitate co/post translational folding
-assist in assembly and disassembly of macromolecular complexes -suppress misfolding and aggregation of unfolded polypeptides -maintain non-native species in "on-pathway" states that remain competent for subsequent folding tot he native state (holding chaperones) |
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How do chaperones recognize unfolded soluble proteins?
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By exposed regions of hydrophobic residues that are normally buried in the interior of the protein.
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How do Hsp 70 chaperones work?
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They interact with hydrophobic residues and use Hsp-40 as their co-chaperone.
They function via cycles of binding and release of proteins, each cycle associated with ATP hydrolysis. |
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What is the alternate name for the Hsp 60 family?
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Chaperonins
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What do they act on?
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They act on proteins that have been fully synthesized but are misfolded.
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How do chaperonins function?
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They take in a misfolded protein and trap them with a GroES cap. Being inside this chaperonin chamber encourages the protein to fold correctly using ATP
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What 3 things can cause normal proteins to unfold?
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The absence of post-translational protein binding partners
Stress Mutations |
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How are proteins that cannot be refolded degraded?
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UPS = Ubiquitin Proteasome System
Enzymes E 1,2,3 help to ubiquitinate the misfolded polypeptide which signals its transport to the proteosome. |
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What are the methods a cell uses to avoid misfolded proteins?
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1) Attempting to refold the protein
2) Attempting to sequester misfolded proteins as aggregates to prevent toxic interactions 3) Elimination via UPS |
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What are CHIP and BAG1?
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Linkers between chaperones and degradation via the proteosome.
They have chaperone interaction domains as well as UPS function domains. |
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How does CHIP work specifically?
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It is an E3 enzyme capable of associating with chaperones Hsp 70 and Hsp 90 and polyubiquinating their substrates.
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How does BAG work specifically?
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It links Hsp 70 to the 26S proteosome to help delivery of the Hsp 70 bound targets to the proteosome for degradation
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What is ERAD?
What does it do? |
Endoplasmic Reticulum associated protein degradation.
It eliminates misfolded or unassembled proteins from the ER (dislocation) to the cytoplasm where they are degraded by UPS |
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What are 2 examples of disease states caused by protein misfolding?
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Phenylketonuria (PKU) - cytoplasm
Cystic Fibrosis - ER |
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What is wrong in cystic fibrosis?
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CFTR, a chloride ion channel on epithelial cells lining the lungs is mutated in more than 70 percent of CF patients. The mutated CFTR protein does not traffic the ER, but is degraded in the cytoplasm. Calcium conduction is not affected.
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What 5 neurodegenerative diseases are caused by insolube amyloid aggregates?
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Amyotrophic lateral sclerosis
Creutzfeld-jacod alzheimers parkinsons amyloidoses |
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What 3 neurodegenerative diseases are caused by polyglutamine repeats in the CNS?
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Huntingtons
Spinocerebellar ataxia Spinal bulbar muscular atrophy |
