1.2 Protein folding Flashcards
What are the protein folding models for small proteins?
- Golf course model
- Pathway model
- Funnel model (most recent - best)
GFP
Explain golf course protein folding model, its pros and cons
- the flat surface shows all the alrternative folding pathways which can be taken to reach the low E stable point (folded protein)
CONS (earliest model):
- protein folding is REVERSIBLE - much E needed to climb back into flat surface -> unlikely model
- the flat surface suggest random searching for the lowest E folding - process would be too long -> unlikely model
Explain pathway protein folding model, its pros and cons
- the starting protein already has lower E point A - the ‘valley’ (defined pathway) directs folding in higher thermodynamic stabilisation towards lowest E point - provides many metastable states
CONS (second model):
- folding is less random than in golf course model because the ‘valley’ speeds up the search of lowest E folding BUT proteins don’t have one defined primary structure (point A) -> unlikely model
What is metastable state?
Short lived stable state (higher in E than stable state - stable not for long)
Explain funnel protein folding model, its pros and cons
- the unfolded protein has many possible folding pathways but the folding is directed under kinetic control into the lowest E point - the stable state
- the unfolding process would need less E as the landscape change is consistent (no steep angles as in golf course model) -> currently accepted model for small proteins
What determines the point the protein reaches on the energy landscape models?
The number of stabilising interactions the protein has formed at a particular point: the more interactions - the more stable - the further folded protein - the lower E point on the landscape
Explain rugged landscape protein folding model, its pros and cons
- rugged landscape suggests E barriers in folding - not as random
- too many pathways are possible than in reality?? idk explore further this model
What are the protein folding models for larger proteins?
- Rugged landscape model
- Moat landscape model
- Champagne glass landscape model
MCR
Explain moat landscape protein folding model, its pros and cons
- suggests different starting positions for folding a single protein
- suggests different folding pathways for a single protein which differ energetically
- ?? explore further this model
Explain champagne glass protein folding model, its pros and cons
- suggests many possible pathways - yet all are energetically identical
- suggests metastable states (stair like decrease in E) of semi-folded protein
What causes protein misfolding?
- gene mutations - change in am. a. - change in interactions - different folding
- translational errors
- post-translational modification errors
- prions - induce misfolding
- random misfolding (due to chance)
What is caused by protein misfolding?
Protein misfolding causes misfunction -> disease
Ex: Huntington’s disease, Parkinson’s disease
Example diseases caused by protein misfolding
- Huntington’s disease (gene mutation -> extended CAG repeats -> misfolding -> protein misfunction)
- Parkinson’s disease (gene mutation -> misfold into α-synuclein fibrils (almost dimeric structures) with hydrophobic parts -> misfoled protein due to new interactions)
What are prions?
Prions - abnormal proteins which cause other proteins to misfold
How does Gibbs free energy of the system change in protein folding?f
ΔG is negative - spontaneous reaction - for thermodynamically favourable protein folding TΔS > ΔH (from ΔG = ΔH - TΔS)
Explain Ramachandran plots
Samples on plots allow to predict secondary protein structure of a particular am. a. based on φ and ψ angles of am. a.of polypeptide chain
https://www.youtube.com/watch?v=aO0l1PReGo0
Which thermodynamic equation must be followed in protein folding?
ΔG = ΔH - TΔS where ΔG < 0
Why does entropy of water increase in protein folding?
When proteins fold they create hydrophobic effect - in folding hydrophobic area interacting with water reduces (hydrophobic fold interacts with another hydrophobic fold) - increase in entropy of water -> net gain in netropy in the system
What is hydrophobic effect?
Hydrophobic effect - the tendency for hydrophobic molecules to isolate themselves from contact with water - water less ordered - increase in ΔS of the system => MAIN DRIVING FORCE OF PROTEIN FOLDING
Explain the energy changes in protein folding, what interactions lead to changes in Gibbs free E
Explain what adds up to each component of ΔG = ΔH - TΔS
+ bond rotation at ΔS
How are planes aligned in alpha helices and beta sheets?
What are the types of non-covalent interactions?
Whatare psi, phi and omega bonds in proteins?
Psi (Ψ) - left to α carbon
Phi (Φ) - right to α carbon
Omega (Ω) - at β C=O carbon between C and N
