Protein folding and misfolding Flashcards
What is protein folding?
The process by which a protein structure assumes its functional shape or conformation.
What was the aim of the Anfinsen experiment?
to determine how proteins folded where for small proteins like RNase A, the information needed for a protein to fold correctly is contained within its amino acid sequence (Anfinsen’s dogma).
Why is protein folding important?
Proper protein folding is crucial for biological function; misfolded proteins can lead to diseases
Give an example of protein denaturation
Cooking an egg:
55% of an egg is ovalbumin
-when cooked, hydrophobic regions are exposed causing coagulation
How could protein folding be described? Why?
cooperative as they are either folded or unfolded.
There is an equilibrium between these states
What are proteopathies?
Diseases caused by the misfolding of proteins, leading to aggregation and toxicity
What is amyloid formation?
The aggregation of misfolded proteins into fibrils, often associated with neurodegenerative diseases like Alzheimer’s
What is Levinthal’s paradox?
The observation that proteins can fold in a time frame much shorter than the theoretical time required to sample all possible conformations.
How can protein folding be studied in vitro?
By using purified proteins in controlled laboratory conditions to observe folding dynamics
What does in vivo mean in the context of protein folding?
The process of protein folding occurring within a living organism, influenced by cellular conditions.
What role do chaperone proteins play in vivo?
They assist in the correct folding of proteins and prevent aggregation.
What are some techniques used for protein purification?
Affinity chromatography, size-exclusion chromatography, and ion-exchange chromatography.
Why is studying protein folding important for understanding diseases?
Misfolding can lead to toxic aggregates, which are implicated in various diseases, including Alzheimer’s.
What is Alzheimer’s disease?
A progressive neurodegenerative disorder characterized by memory loss and cognitive decline.
What is the role of amyloid plaques in Alzheimer’s disease?
They are formed from misfolded amyloid-beta peptides and are a hallmark of the disease.
What is MK-8931 (Verubecestat)?
A small-molecule inhibitor of BACE1, aimed at reducing amyloid production in Alzheimer’s treatment.
What recent advancements have been made in Alzheimer’s treatment?
Successful drug trials have shown promise in slowing mental decline by targeting amyloid production.
What are phi and psi bonds?
Angles of rotation around the peptide bonds that define the conformation of the protein backbone.
What is the significance of the number 198 in protein folding?
It represents the number of different phi and psi bonds in a protein with 100 residues.
How many conformations can a protein theoretically have?
A protein can have an astronomical number of conformations, often exceeding the number of atoms in the universe.
What is the time it takes for a protein to fold?
It can take longer than the age of the universe if all conformations were to be sampled
What is Folding@home?
A distributed computing project aimed at simulating protein folding to understand diseases.
How can individuals support Folding@home?
By signing up to contribute their computer’s processing power to help with simulations.
Why is public awareness important for Alzheimer’s research?
Increased awareness can lead to more funding, research opportunities, and support for affected individuals.
