title: Selection for efficient translation initiation biases codon usage at second amino acid position in secretory proteins.
abstract: The definition of a typical sec-dependent bacterial signal peptide contains a positive charge at the N-terminus, thought to be required for membrane association. In this study the amino acid distribution of all Escherichia coli secretory proteins were analysed. This revealed that there was a statistically significant bias for lysine at the second codon position (P2), consistent with a role for the positive charge in secretion. Removal of the positively charged residue P2 in two different model systems revealed that a positive charge is not required for protein export. A well-characterized feature of large amino acids like lysine at P2 is inhibition of N-terminal methionine removal by methionyl amino-peptidase (MAP). Substitution of lysine at P2 for other large or small amino acids did not affect protein export. Analysis of codon usage revealed that there was a bias for the AAA lysine codon at P2, suggesting that a non-coding function for the AAA codon may be responsible for the strong bias for lysine at P2 of secretory signal sequences. We conclude that the selection for high translation initiation efficiency maybe the selective pressure that has led to codon and consequent amino acid usage at P2 of secretory proteins.
authors: School of Molecular & Microbial Sciences, University of Queensland, St Lucia, QLD 4072.
authors: Yaramah M
authors: YM
authors: Zalucki
authors: Peter M
authors: PM
authors: Power
authors: Michael P
authors: MP
authors: Jennings
mesh_terms: D000596:Amino Acids / Q000032:analysis; D000626:Aminopeptidases / Q000378:metabolism; D003062:Codon / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008239:Lysine / Q000032:analysis / Q000378:metabolism*; D063208:Methionyl Aminopeptidases; D010442:Peptide Chain Initiation, Translational; D021382:Protein Sorting Signals; D021381:Protein Transport
chemical_list: D000596:Amino Acids; D003062:Codon; D029968:Escherichia coli Proteins; D021382:Protein Sorting Signals; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; D008239:Lysine
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