Basic Laws of Chemistry that Drive Protein Folding
Stably folded proteins simultaneously satisfy several basic laws of chemistry including:
Hydrophobic
sidechains
Charged
sidechains
Hydrophobic Amino Acid- will be buried on the inside of the
globular protein, where they are hidden from polar water
molecules.
(+) and (-) will be on the surface of proteins where they often
neutralize each other and form salt bridges.
Polar
sidechains
Polar Amino Acid- will be on the surface of the protein where they
can hydrogen bond with water.
Cysteine
sidechains
Cysteine amino acid-often interact with each other to form covalent
disulfide bonds that stabilize protein structure.
A. What is a disulfide bond?
A single covalent bond between the sulfur atoms in two amino acids called
cysteine.
B. What is the significance of disulfide bonds?
• They are very important in determining the tertiary structure of proteins
• They are very important in determining the quaternary structure of some
proteins.
• A very prominent example would be the role of disulfide bonds in the
structure of antibody molecules.
What is a salt bridge?
Salt bridges fall into the broader category of non-covalent interactions.
A salt bridge is actually a combination of two non-covalent
interactions: hydrogen bonding and electrostatic interactions.
Wild type (left) and mutated (right) form of lamin A. Normally, arginine
(blue) forms salt bridge with glutamate (magenta), but a mutation
results in breaking this interaction (leucine is too short to reach
glutamate) and structure destabilization. At phenotype level this
manifests with progeria syndrome and other genetic mutations.