Lecture 5 - Protein Folding and Quality Control Flashcards
What is the folding pattern of an amino acid dependent on?
Polypeptide Sequence
How can you denature a protein?
You can subject it to extreme conditions by changing its pH, heating it up, putting it in organic solvents, or treating it with chaotropic agents.
What proteins interact with nascent polypeptides to ensure that they correctly form their final conformation?
Molecular Chaperones
What do molecular chaperons do in order to make folding clients take on their native structure?
They use a complex ATP hydrolysis cycle in order to form a pocket that incorporates the folding client, which will allow it to find its appropriate domains so that its structure folds up correctly.
The level of which protein is increased rapidly during a rapid increase in temperature?
Heat Shock Proteins (HSP)
Describe the Hsp70 ATPase cycle.
Hsp70 is open to interact with an unfolded client protein in its ATP-bound state. When the protein comes in, ATP is hydrolyzed to ADP, closing the hydrophobic pocket where it will fold. ATP will bind again to the Hsp70, reopening it so that it releases the folded protein.
What are the differences between Hsp70 and Hsp90?
Hsp90 acts as a dimer (a complex of two identical molecules), is not as prevalent in cells as Hsp70, and is more specific to certain signaling molecules.
What does Hsp90 play a role in?
Hsp90 plays an important role in ensuring that important transcription factors and other signal transduction molecules get correctly folded.
What are chaperonins?
Chaperonins are large, supramolecular machines that are devoted to the folding of specific client proteins, using ATP.
What barrel-shaped mechanisms provide a hydrophobic environment for unfolded client proteins to go in and fold up in a correct native shape?
Chaperonins
What happens if you reduce the Hsp90 dosage in Drosophila to half its normal amount?
The protein folding process will be messed up and underlying genetic variations that were hidden before will surface.
What are “plaques”? What diseases are they typical in?
Plaques are protein aggregates that form in cells (particularly in neurons). They are typical in Alzheimer’s, Huntington’s, Parkinson’s, and ALS.
What is Kuru (or Laughing Death) cause by?
Prions (Proteinaceous Infectious Agents)
What are prions?
Prions (proteinaceous infectious agents) are membrane proteins that are present in all of our cells, but mostly in neuronal cells.
What are the two forms of PrP? What are the differences?
Conformer state PrP is a non-infectious protein that is normally found in body cells. It has a nicely folded conformation consisting of alpha-helices. Non-conformer state (scrapie form) PrP is different in that its alpha-helices are switched to beta-sheets. The scrapie form can cause the conformer state to misfold and accumulate, ultimately leading to cellular dysfunction. As they are resistant and we don’t know how to control them, diagnosis of scrapie form ends with death.
