Almost Indistinguishable, different in function.

If you see 2 amino acid sequence that just a 1-2% slightly different on the sequence, can we just ignore their differences and simply said the protein will be same with the same 3-D confirmation. Don’t simply make the easy conclusion like that because the slightly different can describes a lot.

One such of puzzle is related to the mammalian cytoskeletal protein β- and γ-actin, whose amino acid sequences are 98% identical.  The slightly difference of both protein make they differ in protein modification which β-actin is modified by addition of arginine (arginylation) and γ-actin is not modified, resulting the distinct role for each in the cell.

Scientists try to understand this phenomenon. This is unexpected example of the protein whose the properties are determined at the nucleotide rather than amino acid level, forcing a reassessment of what defines a synonymous change in the gene sequence.

Arginylation of certain protein occur after translation of their termini. Although discover in 40 year ago, the effect of the argynilation is fully understood than other posttranslational modifications. Proteins are arginylated during normal cell growth and in response to stress, and arginylation has been associated with protein degradation in the proteasome. One prominent group of substrates is actin group but not all actin groups are argynilated in posttranslation modification.

Selective modification of the actins is important for normal cell morphology and migration because the absence of arginylation  substantially decrease intracellular actin cellular level and changes its partial segregration.

In this case, the arginylation of β-actin on the posttranslation makes β-actin preferentially localizes at the protruding leading edge of a migrating cell, where rapid actin polymerization pushes the cell’s front forward. There, β-actin is present as a loose and branched arrangement of relatively short actin filaments. By contrast, γ-actin is found in the cell body in dense nonbranched networks and long contractile stress fibers that impart morphological stability and support cell adhesion.

Because of their slightly different of amino acid sequence they affect the rate of translation, and affect their polypeptide modification and also their stability.

What exactly the differences of their amino acid sequences that affect the translation rates.  As mentioned above to explain this is not in amino acids level but in nucleotide levels. The γ-actin contain high frequency of codon that slower the translation but the same region of codon, the alternate codon that coding same amino acid in β-actin is make the translation faster.

Fast translation allows only arginyation, thereby stabilizing the protein. In contrast slow translation allows both arginylation and ubiquitination occur that leading to fast degradation. In conclusions, the synonymous  mutation that encode same amino acid is again not exactly same in the protein comfirmation and modification.