Lecture 4: protein folding and disease Flashcards
For spontaneous protein folding, change in Gibbs free energy is ….. The folded protein must be of higher/lower? energy than the unfolded protein
negative, lower
What are the two ways that protein folding is spontaneous- the energy of the folded protein is lowered
energy contribution of weak interactions and hydrophobic effect promote folded state
Describe the contribution of weak interactions and what part of the Gibbs free equation it affects
The folded protein structure has many non covalent interactions within its structure such as charge to charge, h bonding and numerous vdW interactions which collectively give a large energy stabilisation.
It lowers the value of the delta H- change in enthalpy.
Describe the hydrophobic effect and what part of the Gibbs free equation it affects
This is when the entropy of the system increases when proteins are folded because the hydrophobic chains cluster tightly in the middle shielded by polar and charged chains that can freely form H bonds with water molecules whereas unfolded, the clatharate structures form around hydrophobic side chains which reduces waters h- bonding freedom as they can’t form H bonds in the direction of the non polar solute.
How does the amyloid disease protein start and why does it progress
The amyloid disease protein is a different conformation of the normal brain protein. There is only a small energy barrier preventing the normal protein to unfold and refold into the amyloid conformation which is actually much more stable due to the beta sheet amyloid fibres.. this means that it needs a really large energy to unfold back to the normal protein form
What is the change in intra and intermolecular contacts between native and disease proteins
In the native folded form of the protein, it is stabilised by intramolecular contacts dominantly. In the disease proteins, the intermolecular contacts are dominant which results in lowering G free energy.
What protein will unfold more spontaneous, G= -8 or G= -50
-8 because its the size of the negative number that means thats the energy barrier it needs to overcome. -50 is a bigger number than -8 so that means that is will be more stable because the energy barrier is bigger.
State the 5 steps from native protein to get to fibrils (amyloid fibres)
native protein-> unfolded form-> misfolded-> oligomers (with intermolecular interactions) ->either amorphous aggregates because of H bonds between strands OR Protofibrils-> fibrils (strands in one line that make a super long beta sheet)
