Protein secondary structural types are differentially coded on messenger RNA

Thanaraj, Thangavel Alphonse; Argos, Patrick

doi:10.1002/pro.5560051003

Cited by 152 publications

(126 citation statements)

References 101 publications

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“…2). Indeed, rare codons (read by nonabundant isoacceptor tRNA) are preferentially located in particular regions: encoding the N-terminal end or unstructured regions of proteins, encoding beta-sheets, turns or links between secondary structured regions, links between consecutive domains, or signal peptides of secreted proteins (Thanaraj and Argos 1996;Zalucki et al 2011;Hess et al 2015). To gain insight into the role of rare codons located in specific locations, relevant works are summarized below.…”

Section: Translation Kineticsmentioning

confidence: 99%

Protein folding and tRNA biology

2017

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Polypeptides can fold into tertiary structures while they are synthesized by the ribosome. In addition to the amino acid sequence, protein folding is determined by several factors within the cell. Among others, the folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins, ligands, or the ribosome, as well as by the translocation through membrane pores. Particularly, the translation machinery and the population of tRNA under different physiological or adaptive responses can dramatically affect protein folding. This review summarizes the scientific evidence describing the role of translation kinetics and tRNA populations on protein folding and addresses current efforts to better understand tRNA biology. It is organized into three main parts, which are focused on: (i) protein folding in the cellular context; (ii) tRNA biology and the complexity of the tRNA population; and (iii) available methods and technical challenges in the characterization of tRNA pools. In this manner, this work illustrates the ways by which functional properties of proteins may be modulated by cellular tRNA populations.

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Section: Translation Kineticsmentioning

confidence: 99%

Protein folding and tRNA biology

2017

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“…Similarly, amino acid sequences encoded by rare codons are often associated with domain boundaries (Thanaraj & Argos 1996). This led to the suggestion of two important ideas; the first is that the positioning of abundant or rare codons on the mRNA transcript…”

Section: The Functional Impact Of Codon Optimizationmentioning

confidence: 99%

Synthetic gene design—The rationale for codon optimization and implications for molecular pharming in plants

Webster

Teh

K.‐C.

2016

Biotech & Bioengineering

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Degeneracy in the genetic code allows multiple codon sequences to encode the same protein. Codon usage bias in genes is the term given to the preferred use of particular synonymous codons. Synonymous codon substitutions had been regarded as "silent" as the primary structure of the protein was not affected; however, it is now accepted that synonymous substitutions can have a significant effect on heterologous protein expression. Codon optimization, the process of altering codons within the gene sequence to improve recombinant protein expression, has become widely practised.Multiple inter-linked factors affecting protein expression need to be taken into consideration when optimizing a gene sequence. Over the years, various computer programmes have been developed to aid in the gene sequence optimization process. However, as the rulebook for altering codon usage to affect protein expression is still not completely understood, it is difficult to predict which strategy, if any, will design the 'optimal' gene sequence.In this review, codon usage bias and factors affecting codon selection will be discussed and the evidence for codon optimization impact will be reviewed for recombinant protein expression using plants as a case study. These developments will be relevant to all recombinant expression systems, however, molecular pharming in plants is an area which has consistently encountered difficulties with low levels of recombinant protein expression, and should benefit from an evidence based rational approach to synthetic gene design. This article is protected by copyright. All rights reserved

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“…thermoglucosidasius, without the need to calculate link / end segments (Thanaraj et al, 1996;Angov et al, 2008).…”

Section: Assessing Codon Usage and Predicting A Gene Sequence For Harmentioning

confidence: 99%

Engineering pyruvate decarboxylase-mediated ethanol production in the thermophilic host Geobacillus thermoglucosidasius

Zyl

Taylor

Eley

et al. 2013

Appl Microbiol Biotechnol

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This study reports the expression, purification and kinetic characterization of a PDC from Gluconobacter oxydans. Kinetic analyses showed the enzyme to have high affinity for pyruvate (120µM at pH 5), high catalytic efficiency (4.75 x 10 5 M -1 s -1 at pH 5), a pH opt of approximately 4.5 and an in vitro temperature optimum at approximately 55°C (the highest yet reported for a b a c t e r i a l P D C ) . D u e t o g o o d in vitro thermostablity (approximately 40% enzyme activity retained after 30 minutes at 65°C) this PDC was considered to be a suitable candidate for heterologous expression in the thermophile Geobacillus thermoglucosidasius. Initial studies using a variety of methods failed to detect activity at any growth temperature. However, the application of codon harmonization (i.e., mimicry of the heterogeneous host's transcription and translational rhythm) yielded a protein that was fully functional in the thermophilic strain at 45°C (as determined by enzyme activity, Western blot, mRNA detection and ethanol productivity). Here we describe the successful expression of PDC in a true thermophile. Yields as high as 0.35 g/g ±0.04 ethanol per gram of glucose consumed were detected, highly competitive to those reported in ethanologenic thermophilic mutants. Although activities could not be detected at temperatures approaching the growth optimum for the strain, this study highlights that the possibility that previously unsuccessful expression of pdcs in Geobacillus spp. may be the result of ineffective transcription / translation coupling.

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Protein secondary structural types are differentially coded on messenger RNA

Cited by 152 publications

References 101 publications

Protein folding and tRNA biology

Protein folding and tRNA biology

Synthetic gene design—The rationale for codon optimization and implications for molecular pharming in plants

Engineering pyruvate decarboxylase-mediated ethanol production in the thermophilic host Geobacillus thermoglucosidasius

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