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11 Cards in this Set
- Front
- Back
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How is reinitiation favoured post-translation of the mRNA? |
PABP in Poly A tail (3') have protein-protein interactions with EIF4G on the 5' end of the translated mRNA, forming a circle. This formation increases efficiency as all the components required for initiation are in close proximity of the mRNA and initiation and elongation can be started quickly. |
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What factors stabilize mRNA and make it highly translatable? |
The Poly A tail and EIF4G. The Poly A tail is important for protecting against 3' to 5' exonuclease activity. Longer Poly A tails have more associated PABP proteins which block the exonucleases. The longer the adenosine tail is, the longer it takes for the exonucleases to reach the important transcript. Additionally, the EIF4G on the 5' end interact with PABP to make the Poly A tail more stable by protecting the cap, further blocking the exonucleases and making the transcript even more translatable. |
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How is quality control maintained of mature, exported mRNAs? |
The pioneer round, or first round of translation, is very important. The ribosomal subunit needs t recognize and remove associated SR proteins that are from the nucleus that should have been removed by helicase activity at the nucleopore. At the termination site, there should be no more exons and the Poly A tail should be very close. If the ribosomal complex hits a premature stop, many proteins will be left bound to the mRNA, exons will still be found post termination, and the Poly A tail will be very far away. This creates truncated proteins with half the function of normal proteins that can't perform entire cellular functions, and is a mutation. Nonsense Mediated Decay (NMD) is a cellular process that eliminates these mutated mRNAs. |
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How are polypeptides folded into their functional states? |
During translation, hydrophobic regions of proteins may be suddenly exposed to aqueous solution, which they don't like, and the protein regions curl up into balls. To be functional, the protein must be in its lowest energy conformational, folded state. If we denature the proteins by breaking the hydrogen bonds, and allow to renature by purring in a buffer and removing the hydrogen bond breaking agent slowly, the proteins can refold into their necessary conformation. This is a slow process though, so there are better ways. |
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What are Heat Shock Proteins? |
They are protein chaperones that allow for the immediate folding of proteins post translation so that they can be used. HSP chaperones are activated under heat stress, when proteins may be denatured by heat or can't fold normally. HSP 70 and HSP 90 use ATP to conform to the client protein so that the protein can fold correctly. Then, ATP is hydrolyzed to ADP, resulting in another conformational change which then releases the protein. However, the cycle can continue id there is still the presence of exterior hydrophobic regions in the protein. |
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What are chaperonins? Provide examples. |
Chaperonins are large macromolecular machines that fold specific client proteins. Through ATP binding/hydrolysis with the GroEs cap, they can take proteins into the chamber, use ATP to change conformation so folding is enhanced, and cycle continues until proper folding is achieved. Then it's released. We have the best understanding of GroEL that is bacterial, and we know of TriC in humans. |
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What are some of the diseases that are associated with improper protein folding? |
Alzheimer's Disease: tangles of proteins found in the brains of deceased individuals with the disease. Called Amyloid plaques. Huntington's Disease: Protein aggregates in neurons in the brain which are associated with neural cell death. Unclear if causation or just correlation. Kuru: feared disease of many member of the Fore People, a cannibalistic tribe in New Guinea. Resulted in uncontrollable outbursts of laughter, then eye crossing, then loss of motor capacities. Linked to the eating of diseased peoples as a cultural tradition. Started to see an increase in diseases like scrapies, BSE and Creutzfeld-Jakob which come from proteins called Prions. |
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What are prions and how are they related to Kuru and Creutzfeld-Jakob? |
Everyone has prion proteins, but they come in two states; the conformer which is non infection and has alpha helix structures, and non-conformers, which are infectious and have B-sheet structures. The non-conformer prions can change the conformation of the non-infectious conformers, making them infectious as well with B-sheets. They form plaques together which form fibrals and break and grow over and over. By eating the dead, the Fore people were consuming infectious prions that changed their normal prions and made big holes in their brains. |
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How do proteins to be secreted get transported into the endoplasmic reticulum? |
There is an ER signal sequence that along with ribosome and mRNA make way to ER, where ribosome interacts directly with the ER and translates polypeptides directly into it. Ribosomes on the rough ER allow for membrane transit. |
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How are cysteine residues modified to form disulfide bridges in proteins in the ER? |
ER proteins have to be folded into a particular tertiary structure. This sometimes requires disulfide bridges, and the only places this is possible is in the ER due to the presence of the enzyme protein disulfide isomerase. Thiol groups present in cysteines of the client proteins allow for the disulfide bridges through redox reactions from where the hydrogens are (an oxidized or reduced PDJ) |
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What are the mechanisms for protein quality control in the ER? |
The chaperones BiP and Calreticulin/Calnexin act as important quality controls. They ensure proper folding and prevent aggregation, and bind irreversibly to proteins that did not fold correctly to try to fold them. BiP is present bound to IRE1, which binds 1:1. When BiP binds to unfolded proteins, IRE1 is exposed to dimerize. As a dimer, IRE1 takes on endonuclease activity and can carry out a splicing event on an mRNA that encodes a transcription factor which can increase the expression of chaperones. If this doesn't work, the Unfolded Protein Response is activated, and if this doesn't work, cell death is initiated. |
