New modeling shows how synonymous mutations — those that change the DNA sequence of a gene but not the sequence of the encoded protein — can still impact protein production and function. A team of researchers led by Penn State chemists modeled how genetic changes that alter the speed of protein synthesis, but not the sequence of amino acids that comprise the protein, can lead to misfolding that changes the protein’s activity level, and then corroborated their models experimentally. The results demonstrate the importance of kinetics — the rate of protein synthesis — in addition to sequence for determining protein structure and function and could have implications in fields such as biopharmaceutics for fine tuning the activity of synthesized proteins.
Proteins are composed of long strings of amino acids that then fold up into three-dimensional functional structures. Each amino acid is encoded by a triplet of letters in the DNA alphabet of A, T, C and G called a codon, but there is redundancy built in to the system such that more than one codon can correspond to the same amino acid. Therefore, a mutation that changes the DNA sequence of a gene won’t necessarily change the sequence of the encoded protein if the mutation results in a "synonymous codon." To make a protein, DNA in the nucleus of a cell is first transcribed into a messenger RNA (mRNA). The mRNA is then transported out of the nucleus where it is translated into a nascent protein by a cellular organelle called a ribosome. After translation the protein is folded into its final functional form.