> why doesn't initiation occur also at methionines in the middle of proteins?
It can and does. I can show you expression gels where I make full-length protein and a fragment from an internal initiation. > Why use a big expensive amino acid instead of choosing one of the glycine > codons? > I can't quickly track anything down in the literature to back this up, but "expensive" could be part of it. The cell doesn't want to start translation if there isn't ample resources to finish the job. Perhaps Met concentration is a proxy for anabolic potential of the cell? Or at least was primordially and "QWERTY'd in"? /wild speculation Shane Caldwell McGill University On Tue, Mar 19, 2013 at 9:46 AM, Edward A. Berry <ber...@upstate.edu> wrote: > Opher Gileadi wrote: > >> Hi Theresa, >> >> To add to Anat's comments: Although the AUG codon for the first >> methionine and all other methionines in a protein coding sequence look the >> same, they are read in a very different way by the ribosomal machinery. The >> first AUG is recognized by the initiation complex, which includes the >> separate small ribosomal subunit (40s), a special tRNA-methionine, and >> initiation factors (proteins) including eIF2. This leads to assembly of a >> complete ribosome and initiation of protein synthesis. Subsequently, in the >> process of elongation, AUG codons are read by a different tRNA, which is >> brought to the 80s ribosome bound to a protein called elongation factor 1a. >> This is an oversimplification, of course, but the point is that the >> initiation codon (=the first amino acid to be incorporated to the protein) >> is read by a special tRNA, hence the universal use of methionine. >> >> Opher >> >> Yes, but why methionine? Half the time it has to be removed by > N-terminal peptidase to give a small first residue, or by leader sequence > processing. Why use a big expensive amino acid instead of choosing one of > the glycine codons? Is there an obvious reason, or just "it had to be > something, and Met happened to get selected"? > > And why sometimes alternate start codons can be used? and why doesn't > initiation occur also at methionines in the middle of proteins? I'm > guessing it has to do with 5' untranslated region and ribosome binding > sites. So could the start codon actually be anything you want, provided > there is a strong ribosome binding site there? > > Just being philosophical, and not afraid to display my ignorance, > eab >
