Protein Folding And Stability Flashcards
What causes neurodegenerative diseases?
Incorrect protein folding
Outline cystic fibrosis
-involves the mix folding of a protein called CFTR
-protein regulates the transfer of chloride and sodium across the cell membranes
-disruption of chloride and sodium transfer leads to sticky mucus to build up in the lungs and digestive system
What does the protein CFTR regulate
Transfer of chloride and sodium across the cell membranes
Give examples of diseases associated with improper folded proteins
Alzheimer’s disease
Parkinson’s disease
Huntington’s disease
Cystic fibrosis
What are plaques/ amyloid fibrils?
Deposition of protein aggregates
Reason for correlation of disease increasing with age:
As we age the delicate balance of synthesis, folding and degradation of proteins is disturbed, which results in the production and accumulation of misfolded protein aggregates.
What is CJD
-human prion disease
-neurological disease
-rapid progression
-fatal within 1 year of infection
What is CJD caused by?
An abnormal isoform of a cellular glycoprotein known as the prion protein
What can cause proteins to denature, unfold and aggregate with other misfolded proteins?
A change in pH or an increase in the temperature of the surrounding environment
What are the forces that stabilise the 3D structure of proteins?
-hydrophobic interactions
-ionic interactions
-disulphide bridges
-van der waals
-hydrogen bonding
What is entropy:
A measure of the degree of randomness or disorder in a system
- the total entropy of a system plus that of its surroundings always increases
What are clathrate structures:
When the water molecules come into contact with the non-polar molecules, they form cages (clathrate structures) around them, in an ordered manner compared to water molecules alone
Outline hydrophobic interactions
Non-polar molecules tend to associate with each other in water compared with other less polar solvents. This tendency is called the hydrophobic effect and the associated interactions are called hydrophobic interactions.
What are ionic interactions?
Electrostatic interactions that occur between a positively charged amino acid residue and a negatively charged amino acid residue
What are van der waals
Molecules that do not have a permanent dipole interacting with each other and having an attractive force between those molecules. (Induced dipoles)
Intermolecular forces between atoms and between non-polar molecules as a result of the motion electrons
What is a hydrogen bond
Electrostatic attraction created between a partially positively charged hydrogen atom attached to a highly electronegative atom and another nearby electronegative atom
Type of dipole- dipole interaction
What is an a-helix
Right handed coil of amino-acid residues on a polypeptide chain, typically ranging between 4 and 40 residues. This coil is held together by hydrogen bonds between the oxygen of carbonyl group and the hydrogen of amine group
What is in a beta sheet
Two or more polypeptide chains run alongside each other and are linked in a regular manner by hydrogen bonds between the main chain carbonyl and amine groups
The sheets can have a rippled or pleated appearance. There is no bonding within the chain rather there is bonding across the chain.
What do the polar groups do in an unfolded protein
Hydrogen bonded to and partially surrounded by water molecules
What do the polar groups do in a folded protein
Most polar groups will form one or more intramolecular hydrogen bonds and will be surrounded by the polar and nonpolar groups that make up the interior of a folded protein
What are disulphide bonds
Covalent bonds formed between two cysteine or methionine by oxidation reactions
Not present in the unfolded state but are in the folded state
When did Christian anfinsen conduct his series of experiments?
1950
What are molecular chaperones
A class of proteins that aid in the correct folding of other proteins in vivo
Stabilise unfolded proteins, unfold them for translocation across membranes or for degradation, and/ or to assist in their correct folding and assembly.
Stop newly synthesis proteins from aggregating
