Signal sequence non-optimal codons are required for the correct folding of mature maltose binding protein

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Title Signal sequence non-optimal codons are required for the correct folding of mature maltose binding protein
Author Zalucki, Yarramah; Jones, Christopher E.; Ng, Preston; Schulz, Benjamin L.; Jennings, Michael Paul
Journal Name Biochimica et Biophysica Acta (BBA) - Biomembranes
Year Published 2010
Place of publication Netherlands
Publisher Elsevier
Abstract Non-optimal codons are generally characterised by a low concentration of isoaccepting tRNA and a slower translation rate compared to optimal codons. In a previous study, we reported a 20-fold reduction in maltose binding protein (MBP) level when the non-optimal codons in the signal sequence were optimised. In this study, we report that the 20-fold reduction is rescued when MBP is expressed at 28 degrees C instead of 37 degrees C, suggesting that the signal sequence optimised MBP protein (MBP-opt) may be misfolded, and is being degraded at 37 degrees C. Consistent with this idea, transient induction of the heat shock proteases prior to MBP expression at 28 degrees C restores the 20-fold difference, demonstrating that the difference in production levels is due to post-translational degradation of MBP-opt by the heat-shock proteases. Analysis of the structure of purified MBP-wt and MBP-opt grown at 28 degrees C showed that although they have similar secondary structure content, MBP-opt is more resistant to thermal unfolding than is MBP-wt. The two proteins also exhibit different tryptic fragment profiles, further confirming that they are folded into conformationally different states. This is the first study to demonstrate that signal sequence non-optimal codons can influence the folding of the mature exported protein.
Peer Reviewed Yes
Published Yes
Alternative URI
Volume 1798
Issue Number 6
Page from 1244
Page to 1249
ISSN 0005-2736
Date Accessioned 2010-07-21
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Protein Trafficking
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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