Nucleic Acids Research Advance Access originally published online on August 23, 2007
Nucleic Acids Research 2007 35(17):5748-5754; doi:10.1093/nar/gkm577
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Nucleic Acids Research, 2007, Vol. 35, No. 17 5748-5754
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Selection for efficient translation initiation biases codon usage at second amino acid position in secretory proteins
1School of Molecular & Microbial Sciences, University of Queensland, St Lucia QLD 4072 and 2Molecular Infectious Diseases Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom OX3 9DU
*To whom correspondence should be addressed. Tel: 61 7 33654879; Fax: 61 7 33654620; Email: jennings{at}uq.edu.au
Received May 29, 2007. Revised July 2, 2007. Accepted July 13, 2007.
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.