Question

All polypeptide synthesis starts with the codon AUG bringing methionine at the very first position at the N terminal but, examination of many biological and functional proteins in the cell, when sequenced, does not reveal the presence of methionine at the very first position at the N-terminal. Why and how could this be possible? Explain.

Answer 1

Almost all nascent polypeptides are start with methionine, but not all proteins. After translation, polypeptides undergo post translational modifications and folding in order to become an active proteins. Not every protein necessarily starts with methionine, however the first amino acid methionine will be removed in later processing of the protein. Proteins might be cleaved by a protein-cutting enzyme, protease, at a specific place or have a few of its amino acids altered.

The N-terminal of many polypeptides are removed by post translational modification events, revealing the second or third encoded as the new N-terminus of active protein. That is why all proteins are not begin with aminoacid methionine.