The efficiency of folding of some proteins is increased by controlled rates of translation in vivo

Purvis, Ian J.; Bettany, A. J. E.; Santiago, T.C.; Coggins, John R.; Duncan, Kenneth; Eason, R.W.; Brown, Alistair J. P.

doi:10.1016/0022-2836(87)90230-0

Cited by 181 publications

(131 citation statements)

References 36 publications

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“…These observations led to the postulation made almost 30 years ago, which claims that the rates at which regions of polypeptides are translated affect protein folding, and that gene sequences have evolved to temporally separate the synthesis of defined domains of proteins (Purvis et al 1987). In recent years, this subject has gained great attention from the scientific community; however, a deep understanding of the role of the translation kinetics on protein folding remains unclear (Kirchner et al 2017) (Fig.…”

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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“…Alternatively, translational pausing may occur when rarely used codons are encountered with low abundance of cognate tRNA. An appealing hypothesis suggested earlier by Purvis et al [3] was pursued by Thanaraj and Argos [4]. They proposed that translationally slow regions may coincide with domain termini and linking regions between domains thus facilitating cotranslational folding.…”

Section: Introductionmentioning

confidence: 99%

Expression of different coding sequences in cell‐free bacterial and eukaryotic systems indicates translational pausing onEscherichia coliribosomes

2000

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Five different coding sequences of bacterial or eukaryotic origin in plasmids under the T7 promoter were expressed in a cell-free system derived from Escherichia coli. Translation on E. coli ribosomes resulted in a full-length product only in four of the five coding sequences tested. A unique pattern of less than full-length polypeptides was generated in each case. Many of these polypeptides on E. coli ribosomes reacted with a puromycin derivative, cytidylic acid-puromycin, which was radioactively labeled. Thus these incomplete polypeptides can be defined as nascent peptides bound to the ribosomal P site. Certain nascent peptides could be shifted into full-length protein indicating that they resulted from translational pausing. In contrast to these results, expression of the same coding sequences in a wheat germ or reticulocyte cell-free system resulted in a 809 0% full-length product with no evidence for nascent polypeptides and translational pausing. ß

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“…Indeed, this is exactly what happens in certain cases, as the variability in the rates at which individual amino acids are covalently attached to the C-terminus of the elongating nascent polypeptide chain can strongly influence whether a protein cotranslationally folds and attains its functionality, or misfolds [2][3][4][5][6][7] . The evidence to date indicates that slowing down translation tends to increase cotranslational folding, and simple arguments suggest that this inverse relationship may be a general phenomenon 8 . Protein folding is a stochastic process, and slower codon translation rates afford a domain extra time to fold during translation.…”

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Kinetic modelling indicates that fast-translating codons can coordinate cotranslational protein folding by avoiding misfolded intermediates

O’Brien

Vendruscolo

2014

Nat Commun

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It has been observed for several proteins that slowing down the rate at which individual codons are translated can increase their probability of cotranslational protein folding, while speeding up codon translation can decrease it. Here we investigate whether or not this inverse relationship between translation speed and the cotranslational folding probability is a general phenomenon or if other scenarios are possible. We first derive chemical kinetic equations that relate individual codon translation rates to the probability that a domain will fold, populate an intermediate or misfold, and examine the cotranslational folding scenarios that are possible within these models. We find that speeding up codon translation through misfolding-prone segments can, in some cases, increase the folding probability of a domain immediately before the nascent protein is released from the ribosome and decrease its chances of misfolding. Thus, for some proteins fast-translating codons could be as important as slow-translating codons in coordinating cotranslational protein folding.

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The efficiency of folding of some proteins is increased by controlled rates of translation in vivo

Cited by 181 publications

References 36 publications

Protein folding and tRNA biology

Protein folding and tRNA biology

Expression of different coding sequences in cell‐free bacterial and eukaryotic systems indicates translational pausing onEscherichia coliribosomes

Kinetic modelling indicates that fast-translating codons can coordinate cotranslational protein folding by avoiding misfolded intermediates

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