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closeN-end rule?
Posted by ralmeida on 01 Jun 2009 at 17:41 GMT
I find it surprising that the author does not mention the widely known N-end rule as an alternative hypothesis. The work of Alexander Varshavsky and others has shown that the choice of N-terminal residue has a dramatic impact on protein stability in organisms ranging from bacteria to mammals. This is a distinct effect from translation initiation since it can lead to formation of N-degrons and consequent ubiquitin-mediated proteolysis. Ala or Gly are considered N-end stabilizing residues, which could be a contributing factor to high gene expression. This is consistent with over-representation of GCN and GGN at the second codon.
RE: N-end rule?
xxia replied to ralmeida on 02 Jun 2009 at 03:10 GMT
I am not sure of your logic. You seem to suggest that the observation of frequent use of Ala and Gly codons right after the initiation methionine codon is due to their contribution to protein stability. To put it more explicitly, your logic seems to be as follows. First, most proteins need to have a stabilizing N-terminal. Second, Ala and Gly contribute to a stabilizing N-terminal. Therefore, Ala and Gly codons are used often right after the initiation methionine codon, and contribute significantly to the prevalence of +4G. This logic has at least two problems. First, it is weak to assume that most proteins require a stabilizing N-terminal. Second, even if they do, it is difficult to explain why Val codons are not frequently used after the initiation methione codon (Val at the N-terminal is strongly stabilizing according to Alexander Varshavsky).