Prevalence of prime mass residues in single point mutations and their importance to protein stability, function and...

Prime mass amino acids residues, assigned based upon the nominal mass of their repeating structure in peptides and proteins, provide a more rigid physicochemical definition not achieved with other more common classifiers. Found to occur more often than by chance, the nine prime residues are predominantly hydrophobic in character that play an important role in protein stability and folding. A global study of the prevalence of particular single point mutations across several hundred proteins has revealed that mutations which retain a prime mass residue are favoured over those that lose them. Further, the mutation of a non-prime to prime residue is favoured over the retention of a non-prime residue. The introduction of the prime alanine residue, in particular, is found to occur in over 50 % of cases when a prime or non-prime residue mutates, based on data extracted across almost 16,000 mutations for within a wide range of proteins. Mutation to the prime residues isoleucine (I) and leucine (L), threonine (T) and proline (P) are also found to predominate. This is evident across the many hundreds of database entries and within a single transmembrane protein previously identified to be among the richest-prime residue protein known. Consideration is given to the impact of these observations on protein stability and the advantages they confer to protein evolution. It is shown that the majority of prime residues are recruited early in the development of the genetic code. Last common universal ancestral (LUCA) proteins are enriched in smaller molecular weight, hydrophobic prime amino acids rather than larger aliphatic non-prime ones.