Question

Some proteins, once folded “associate” to form higher order structures (i.e., quaternary structure). Within these structures the single protein chain is known as a “subunit” (not to be confused with a protein domain). If two identical protein chains fold and associate, the quaternary structure is named “homodimer” (and the individual subunits are sometimes referred to as “monomers”); for three “homotrimer” and so on. If, on the other hand, the two protein chains that associate have different primary structures, the quaternary structure is named “heterodimer”. Using the dimer as an example, we know that the respective regions of the protein subunit surfaces that are interfaced, are responsible for the “favorable energy of interaction” which stabilizes the dimeric protein complex.

(a). Although, noncovalent bonding interactions are used both for stabilization of the folded protein molecule and its dimerization, the contribution of the “hydrophobic effect” to chain folding is significantly greater than its contribution to subunit association. Define the “hydrophobic effect” and explain why you would expect it to have a more pronounced role in chain folding compared to dimerization of the folded molecules.

(b) As the protein chain folds to the native structure, it loses entropy. Upon dimerization, more protein entropy is lost. Compare and contrast the source of protein entropy loss, which occurs with folding, with that which occurs with dimerization.