Protein Structure and Folding Flashcards
What are domains in relevance to protein structure?
They are responsible for a particular function or interaction
What is a motif?
A sequence or structural element that contributes to the primary sequence of proteins.
Two examples of proteins having quaternary structure
HIV Protease and Potassium Channel
What is the impact of AlphaFold?
Predicts the protein structure
What is the impact of PandaOmics?
This provides the protein of interest
What is the impact of Chem42?
Generates molecules based on the structure provided by AlphaFold
How do chaperone proteins help?
They form disulfide bonds, protect hydrophobic clusters from aggregation, and interconvert prolyl cis/trans peptide bonds.
What are molecular chaperones?
These help proteins who are struggling to reach their native states by assisting protein folding
T/F: Molecular chaperones interact with native proteins
FALSE
What happens if protein folding not possible?
These proteins would become targeted for protein degradation to maintain protein homeostasis
What are two pathways in which protein degradation occurs in?
Ubiquitin proteasome system(UPS) or the autophagy-lysosome pathway.
Does entropy favor folded or unfolded state of proteins
Unfolded because this creates more disorder.
How to measure stability of protein?
Kf = [Folded]/[Unfolded]
What is protein folding
Polypeptide chain goes from linear chain to native, folded tertiary structure
What is the significance of negative delta G?
Decrease in free energy for a process(reaction is favorable)
What does delta H represent?
Change in enthalpy, meaning this reflects the number and kinds of chemical bonds in reactants and products
What does delta S represent?
Change in entropy, an increase in disorder gives a positive number = favorable
What are prions?
Type of infections agent that doesn’t carry any genetic material
How many domains does the CFTR posess?
5 domains
What are the 5 domains of the CFTR?
2 transmembrane domains(containing 6 hydrophobic alpha helices)
2 nucleotide binding domains(ATP)
1 regulatory domain that contains many phosphorylation sites
What is the most prevalent mutation that affects 80% of CF patients?
DeltaF508
What is the impact of deltaF508?
Reduces thermal and kinetic stability of NBD1, which prevents interdomain interactions
What are the three defects of F508del-CFTR?
1) Inhibits trafficking
2) Enhances degradation
3) Reduces CFTR membrane channel function
How many classes of CFTR mutations are there?
6 classes
What is the purpose of Class 1 CFTR?
Rescue protein synthesis
What is the purpose of Class 2 CFTR?
Correct protein folding
What is the purpose of Class 3 and 4 CFTR?
Restore channel conductance
What is the purpose of Class 5 CFTR?
Maturation/ Correct any splicing errors
What is the purpose of Class 6 CFTR?
Promote protein stability
What are the 3 main types of protein structure modulators?
Potentiators, Correctors, and Amplifiers
What is the role of the potentiator?
Holds the CFTR chloride gate open(Ivacaftor does this)
What is the role of the corrector?
Helps CFTR protein form the correct 3D shape so it can move towards the cell surface(Lumacaftor and Tezacaftor)
What is the role of the amplifier?
Increase the amount of CFTR protein that the cell makes
What is the purpose of CFTR?
a protein that plays a crucial role in maintaining the balance of salt and water on the surfaces of various epithelial cells in the body. Its primary function is to regulate the flow of chloride ions (Cl-) in and out of these cells, which, in turn, affects the movement of water across cell membranes.
