Protein folding and Stability

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How is CF related to protein folding?
CF involves misfiling and results lack of a protein involved in cl- transport across membranes.
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What other nuerodegenerative disorders involve abnormal protein aggregation?
Prion diseases, alzheimer's and parkinson's. These can associate with similar chains to form toxic aggregates.
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How do proteins fold?
Not their energetically most favourable conformation. Interactions with solvent play a major role in folding.
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Protein stability...
Most proteins are marginally stable however many are easily denature at extremes of pH. Proteins are easily denatures and work best at the optimum growth temp of the organism from which they were isolated from. Not stable in organic solvent as no h2o
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What are the forces that hold the 3D structure of proteins?
Hydrophobic, ionic, van der waals, hydrogen bond, disulphide bonds ( only covalent)
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Hydrophobic Interactions
These are amino acids side chains that are non polar and are usually found on the inside of globular proteins. These include alanine, isoleucine, phenylalanine and tryptophan.
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What is the physical basis for the hydrophobic effect?
As non-polar can't form hydrogen bonds with the water. This causes a clathrate structure to form a crystalline structure round it.
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Why does oil aggregate in water?
ΔG= ΔH-TΔS It is entropically unfavourable to make contact with water and the most energetically favourable thing to do is aggregate.
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Why does protein folding occur in water then?
As it minimises the contact with water for the hydrophobic residues.
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Ionic interactions (salt bridges)
Electrostatic interactions occur between amino acids with opposite charges, These can be between a pair or multiple clusters of interactions.
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What is an ion pair network?
Where subunits of several charged residues all join together. Solvents sometimes hydrate the ionic bonds, meaning they aren't always strong.
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Van der Waals interactions
These are non covalent interactions between electrically neutral molecules that arise from the electrostatic interactions between permanent dipoles and instantaneous.
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How strong are van der waals forces?
much weaker than ionic but there are many of them. They do have a +/- element but there is an optimal distance between the repulsive and attractive energy.
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Why do atoms pack regularly
as optimal packing maximises van der Waals forces.
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Hydrogen bonds
These are more weak electrostatic interactions between a weakly acidic donor and acceptor.
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What is the ideal bond length of a H bond
2.7-3.1A
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a-helix
Right handed helix, 3.6 residues a turn, pitch is 5.4A, C=O bond (n) bonds with the N-H bond (n+4). The H bond is 2.8A. R-groups out. Average length of 11 residues in glob proteins.
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How do proteins hydrogen bond in the unfolded state?
With water, which is then liberated once folded.
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Disulfide bonds
covalent between two cysteine amino acids. The only covalent bond. Mainly found in proteins exported from the cell and in hyperthermophilic proteins which have to be stable at high temps.
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how is a disulphide bond formed?
Oxidation of -SH
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How do proteins fold?
From their primary sequence, but folding is not fully understood and difficult to predict.
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How looked at protein folding and what did they find? (ribonuclease)
Christian B. Anfinsen. He found generally proteins fold spontaneously with a native conformation being the mot energetically stable.
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Anfinsens experiment... what did he do?
He denatured it with B-mercaptoethanol and urea. When urea and B-metacaptoehtanol were remove together 100%activity. When B then urea only 1% activity restored.
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What did Anfinsens experiments show?
That proteins are able to fold on their own. This is because the protein is scrambled and many incorrect combinations of disulphide bonds are made. Proteins can fold spontaneously, sequence dictates structure.
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Levinthal Paradox
If each aa has 10 conformations and tries combinations with other aa. Time =10^n/10^13(time it take for each). Then a protein of 100 aa would take 10^87 seconds. (too long)
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What does the levinthal paradox show?
That theres not enough time for the aa to do this, so the they fold to their native conformations by directed pathways rather than random search methods.
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What are chaperonins?
Proteins that help proteins to fold. It is a nice environment to keep interfering proteins away.
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Card 2

Front

What other nuerodegenerative disorders involve abnormal protein aggregation?

Back

Prion diseases, alzheimer's and parkinson's. These can associate with similar chains to form toxic aggregates.

Card 3

Front

How do proteins fold?

Back

Preview of the front of card 3

Card 4

Front

Protein stability...

Back

Preview of the front of card 4

Card 5

Front

What are the forces that hold the 3D structure of proteins?

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