Protein families arise when a protein sequence that generates a stable fold diverges over many generations and acquires new functions. One example of this can be seen in the globin family

Question

Myoglobin is a stable monomeric protein that can help carry oxygen using a heme molecule. Hemoglobin is stable as a tetramer. It also carries oxygen through the use of heme groups, but it is useful over a much more dynamic range of oxygen than myoglobin. The "globin fold" is structurally conserved across these proteins, but the ability to tetramerize arose through genetic drift and natural selection. Provide an explanation for how the globin sequence can change and still produce the same overall fold. Support your explanation by suggesting the location and type of sequence alterations that might have little effect on the overall protein fold, but may favor the formation of a multisubunit protein.

Answer 1

Amino acids that are found on the surface of a folded monomeric protein are the best candidates for mutations. Because they are on the surface of the protein, the side-chain interactions are not important for forming the structural core. If alternative amino acids are polar, they can interact equally well with the aqueous environment. It is likely that the sequence comparisons between myoglobin and the ?/? globins will reflect changes of surface residues. Furthermore, we may predict that if the surface amino acids changed from polar amino acids to nonpolar amino acids, this would promote multimerization. Nonpolar residues would interact with each other rather than the polar molecules in the cytosol.