Wednesday, 25 January 2017
PROTEIN FOLDING AND STABILITY
Once a polypeptide is made, it then folds into its characteristic three-dimensional shape.
As the protein folds, initial interactions then initiate further interactions –called the
cooperativity of folding.
Folding occurs in less than a second.
Protein folding and stabilization depend upon noncovalent forces, including the hydrophobic
effect, hydrogen bonding, van der Waals interactions, and charge-charge
Although individually weak, collectively they are strong.
The weakness gives the protein flexibility to change conformations.
Once in place, the collective effect keeps the protein in its proper shape.
No actual protein folding pathway is known, however, the structure of some intermediates
has been described.
It appears that hydrophobic effects are very important initially, such that the
protein “collapses” onto itself.
Then some parts of secondary structure begin to form.
Then motifs form, followed by the stable, completely folded protein.
The Hydrophobic Effect
Proteins are more stable when their hydrophobic R-groups are in the interior of a protein
and away from water.
Nonpolar side chains then interact with each other.
Polar side chains remain in contact with water on the protein surface.
Hydrogen bonds in a helices, b sheets and turns form first as a protein folds _ defined
regions of secondary structure.
Many hydrogen bonds ultimately form between polypeptide backbone and water, between
backbone and R-groups, between R-groups, and between R-groups and water.
Those hydrogen bonds within interior of protein are more stable than those on the surface
because these bonds do not then compete with water molecules.
Van der Waals Interactions and Charge-Charge Interactions
Van der Waals contacts between nonpolar side chains are also important.
Charge-charge interactions contribute minimally to protein stability because most ionic
bonds are found on the surface of a protein.
Protein folding does not involve a random search for the proper conformation.
Secondly, the final shape of a protein is dependent upon its primary structure.
Small proteins can fold properly in vitro, but larger ones need the help of molecular
Chaperones are proteins that assist with protein folding by binding to proteins before they
are completely folded.
They prevent the formation of incorrectly folded intermediates that may trap a polypeptide
into an improper form.
They also bind to protein subunits and prevent them from aggregating and precipitating
before then are assembled into a multisubunit protein.
Most chaperones are heat-shock proteins. Originally found when cells were subjected to
temperature stress, which tends to make proteins denature.
The major heat-shock protein is HSP-70, present in all eukaryotes and prokaryotes.
Most highly conserved protein known _ indicates the very important role of HSP-70
Chaperones usually bind to the hydrophobic portions of a protein and prevent them from
interacting with water or at least coming into contact with water molecules.