In vitro protein synthesis: chain initiation.

Abstract

The start signal, for chain initiation, specifies at a minimum N-formylmethionine and perhaps even N-formylmethionyl-alanyl-serine. Its importance lies not only in the fact that there is a unique series of nucleotides meaning "start here", but also in the fact that these nucleotides lead to the incorporation of an amino acid with a blocked amino group. This kind of a start has numerous consequences. It would impose a direction on protein synthesis. It would preclude the coupling of polypeptides specified by a polycistronic message, regardless of the nature of "stop" codons. Similarly, it would preclude coupling of polypeptides when nonsense codons, assumed to be homologous to stop codons, are suppressed. It would explain why such nonsense codons, when not suppressed, lead only to the production of an N-terminal fragment, since peptide synthesis can not restart. It would predict the existence of another, perhaps suppressible, class of nonsense mutations[long dash]mutations to the N-formylmethionine codon in the middle of a gene. These mutations would probably result in the production of two peptide fragments. By leading to polypeptide chains that may require trimming prior to being able to function, it would offer a new dimension to the control, in time and space, of protein function.