> 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"?
That makes sense.
Also, It occurred to me after posting that the Met is not necessarily wasted
if it gets cleaved off by N-peptidase. It can get loaded onto another tRNA and
go through the cycle again. presumably the cost in ATP for loading Met-tRNA
and gly-tRNA is the same.
Maybe Met makes a better "handle" for some step in initiation.
Shane Caldwell wrote:
> 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 <[log in to unmask] <mailto:[log in to unmask]>> 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
>
>
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