Protein DLA -Structure And Function Flashcards
What is protein folding?
Folding allows formation of the native(functional) protein form
What processes do protein folding depend on?
Folding is a trial and error process that depends on :
- Composition of side chains
- Hydrogen bonding
- Disulfide bonds
The - Ionic interactions
- Hydrophobic effect
- All in the context of repulsion of some shapes(steric, charge, bond angle constraints)
What is the purpose of protein folding?
To result in the most stable or favorable structure
Outline the process of protein folding
- Formation of secondary structures
- Formation of domains
- Formation of final protein monomer
Denaturation is usually….
Irreversible
In rare cases, denaturation is reversible (RNAse A)ribonuclease A
What is lost due to denaturation?
- loss of biological activity
- all other shape / conformational structure
How does denaturation affect primary structure?
Primary structure stays intact
List some denaturation agents
- heat
- organic solvents
- mechanical shearing
- heavy metals
- detergents
- chaotropic
- drastic change in pH
Where can RNAse be found?
On the hand
What happens if denaturing agents are removed from RNAse after it is denatured?
RNAse, forms right back
What are Chaperones?
Molecules that prevent inappropriate protein to protein interactions by:
- keeping unfolded proteins separate
- enhance folding rate
- Protect side chains from inappropriate interactions
What are Heat Shock Proteins?
A special type of chaperone
What is the purpose of Heat Shock Proteins?
Their synthesis increases in response to high temperature and other conditions which increase protein denaturation in the cell e.g. HSP70
What are proteases?
Enzymes that degrades the protein
How do protease break down proteins?
Breaking the peptide bond
What may cause non-enzymatic protein degradation?
- Very low pH or very high pH
- Heat
- Time
- doesn’t happen naturally
Does protein degradation occur in the stomach? Why?
Does not occur in the stomach.
The pH is not low enough, Heat is not high enough and not enough time
What happens to dietary protein in the stomach?
Dietary protein is not degraded, but it is denatured
- denatured means the proteins unfolds
- loss of conformation/shape
What is the job of the stomach?
To denature proteins, so they are easier to degrade by digestive enzymes
What are chemicals and conditions that promote protein denaturation, giving a reason for each
- Heat, pulls stuff apart
- stuff that alters changes ionic bonds and hydrogen bonding( e.g. salt, acid, base)
- detergent which allows hydrophobic areas to interact with water
- reducing agents which can break disulfide bonds
Detergents are _________ molecules
Amphipathic
Give an example of a detergent that can denature proteins
SDS- sodium dodecyl sulfate
What is sodium dodecyl sulfate used for?
SDS is in toothpaste
What is another name for beta-mercaptoethanol?
Ethanol thiol
How can mercaptoethanol be used to remove disulfide bridges and restore cysteine molecules?
Addition of urea and mercaptoethanol break cystine bridges and acts as a reducing agent
Removal of urea and mercaptoethanol restores disulfide cross-links correctly
Give two examples of misfolded proteins that are resistant to degradation, causing diseases
- Prion disease
- Alzheimer disease
What may increase protein misfolding?
Some genetic variants(mutation) might increase likelihood
Explain how protein misfolding leads tho Ahlzeimers
- Amyloid-B protein undergoes proteolytic cleavage as a part of normal degradation
- A non-toxic fragment may be created, which is cleared and disposed of
- A neurotoxic form may be created, this accumulates and will eventually lead to Ahlzeimer’s which is degrade-resistant- this accumulation causes aggregation with other proteins, such as tau, which cause neurofibrillary tangles and death of brain regions
Describe the structure and effect of the fibrous Amyloid protein
The twisted B-pleated sheet fibrils have 3d structure that resembles silk fibrils
Supposed to be globular protein but becomes fibrous which the brain cannot degrade fast enough
Give prison disease examples
- Scrapie in sheep(sheep scraping flesh and hair)
- creutzfeldt-Jacob disease in humans
- mad cow disease
All mammals have…
The prion protein (PrP)as a normal brain protein(unknown function)
What does prion stand for?
Protianacious infectious particle
What is the normal shape of the prion protein?
The normal protein is the PrPc(prion protein cellular)
How can PrPc indirectly cause Scrapie in sheep?
The PrPc can change shape to become a disease causing form called, PrPSc (Prion protein-scrapie)
What happens when PrPc become PrPSc?
- Predominant beta sheet
- Super-duper resistant to degradation
- damages neuron (scrapie in goats)
Why is PrPSc called transmissible/ one of the transmissible spongiform encephalopathies?
Because if you ate someone’s brain who had PrPSc it would cause your normal PrPc into PrPSc
How much PrPSc to convert your PrP into the disease state?
Only one, because it’s accumulation will cause damage to brain tissue
Formation of one PrPSc cause conversion of all PrPc to take the form of PrPSc
“Catalytic conversion”
