scholarly journals First-principles model of optimal translation factors stoichiometry

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jean-Benoît Lalanne ◽  
Gene-Wei Li
Keyword(s):  
First Principles ◽  
Rational Design ◽  
Mrna Translation ◽  
Central Process ◽  
Growth Optimization ◽  
Translation Factors ◽  
Diffusion Constants ◽  
Quantitative Understanding ◽  
Flux Model ◽  
Enzymatic Pathways

Enzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here we report a biophysical, first-principles model of growth optimization for core mRNA translation, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that predictions from maximization of ribosome usage in a parsimonious flux model constrained by proteome allocation agree with the conserved ratios of translation factors. The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion constants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry.

scholarly journals First-principles model of optimal translation factors stoichiometry

2021 ◽  
Author(s):  
Jean-Benoît Lalanne ◽  
Gene-Wei Li
Keyword(s):  
First Principles ◽  
Rational Design ◽  
Mrna Translation ◽  
Central Process ◽  
Growth Optimization ◽  
Translation Factors ◽  
Diffusion Constants ◽  
Quantitative Understanding ◽  
Flux Model ◽  
Enzymatic Pathways

AbstractEnzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here we report a biophysical, first-principles model of growth optimization for core mRNA translation, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that a parsimonious flux model constrained by proteome allocation is sufficient to predict the conserved ratios of translation factors through maximization of ribosome usage The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion constants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry.

First-principles study of the impact of chemical doping and functional groups on the absorption spectra of graphene

2021 ◽  
Author(s):  
Iyyappa Rajan Panneerselvam ◽  
Pranay Chakraborty ◽  
qiong nian ◽  
Yongfeng Lu ◽  
Yiliang Liao ◽  
...  
Keyword(s):  
Absorption Spectra ◽  
First Principles ◽  
Silicon Germanium ◽  
Rational Design ◽  
Dielectric Constants ◽  
Flat Band ◽  
Chemical Doping ◽  
Optical Processing ◽  
Electronic Band ◽  
The Impact

Abstract The rational design of the electronic band structures and the associated properties (e.g., optical) of advanced materials has remained challenging for crucial applications in optoelectronics, solar desalination, advanced manufacturing technologies, etc. In this work, using first-principles calculations, we studied the prospects of tuning the absorption spectra of graphene via defect engineering, i.e., chemical doping and oxidation. Our computational analysis shows that graphene functionalization with single hydroxyl and carboxylic acid fails to open a band gap in graphene. While single epoxide functionalization successfully opens a bandgap in graphene and increases absorptivity, however, other optical properties such as reflection, transmission, and dielectric constants are significantly altered. Boron and nitrogen dopants lead to p- and n-type doping, respectively, while fluorine dopants or a single-carbon atomic vacancy cannot create a significant bandgap in graphene. By rigorously considering the spin-polarization effect, we find that titanium, zirconium, and hafnium dopants can create a bandgap in graphene via an induced flat band around the Fermi level as well as the collapse of the Dirac cone. In addition, silicon, germanium, and tin dopants are also effective in improving the optical characteristics. Our work is important for future experimental work on graphene for laser and optical processing applications.

scholarly journals Molecular mechanisms for the control of translation by insulin

1997 ◽  
Vol 328 (2) ◽  
pp. 329-341 ◽  
Author(s):  
G. Christopher PROUD ◽  
M. Richard DENTON
Keyword(s):  
Ribosomal Protein ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Chain Elongation ◽  
S6 Kinase ◽  
Ribosomal Protein S6 ◽  
Translation Factors ◽  
Specific Mrnas

Insulin acutely stimulates protein synthesis in mammalian cells, and this involves activation of the process of mRNA translation. mRNA translation is a complex multi-step process mediated by proteins termed translation factors. Several translation factors are regulated in response to insulin, often as a consequence of changes in their states of phosphorylation. The initiation factor eIF4E binds to the cap structure at the 5ʹ-end of the mRNA and mediates assembly of an initiation-factor complex termed eIF4F. Assembly of this complex can be regulated by eIF4E-binding proteins (4E-BPs), which inhibit eIF4F complex assembly. Insulin induces phosphorylation of the 4E-BPs, resulting in alleviation of the inhibition. This regulatory mechanism is likely to be especially important for the control of the translation of specific mRNAs whose 5ʹ-untranslated regions (5ʹ-UTRs) are rich in secondary structure. Translation of another class of mRNAs, those with 5ʹ-UTRs containing polypyrimidine tracts is also activated by insulin and this, like phosphorylation of the 4E-BPs, appears to involve the rapamycin-sensitive signalling pathway which leads to activation of the 70 kDa ribosomal protein S6 kinase (p70 S6 kinase) and the phosphorylation of the ribosomal protein S6. Overall stimulation of translation may involve activation of initiation factor eIF2B, which is required for all initiation events. This effect is dependent upon phosphatidylinositol 3-kinase and may involve the inactivation of glycogen synthase kinase-3 and consequent dephosphorylation of eIF2B, leading to its activation. Peptide-chain elongation can also be activated by insulin, and this is associated with the dephosphorylation and activation of elongation factor eEF2, probably as a consequence of the insulin-induced reduction in eEF2 kinase activity. Thus multiple signalling pathways acting on different steps in translation are involved in the activation of this process by insulin and lead both to general activation of translation and to the selective regulation of specific mRNAs.

scholarly journals Activation of mRNA translation in rat cardiac myocytes by insulin involves multiple rapamycin-sensitive steps

2000 ◽  
Vol 278 (4) ◽  
pp. H1056-H1068 ◽  
Author(s):  
Lijun Wang ◽  
Xuemin Wang ◽  
Christopher G. Proud
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Glycogen Synthase ◽  
Mrna Translation ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Translation Factors ◽  
P70 S6k ◽  
Eef2 Kinase

Insulin acutely activates protein synthesis in ventricular cardiomyocytes from adult rats. In this study, we have established the methodology for studying the regulation of the signaling pathways and translation factors that may be involved in this response and have examined the effects of acute insulin treatment on them. Insulin rapidly activated the 70-kDa ribosomal S6 kinase (p70 S6k), and this effect was inhibited both by rapamycin and by inhibitors of phosphatidylinositol 3-kinase. The activation of p70 S6k is mediated by a signaling pathway involving the mammalian target of rapamycin (mTOR), which also modulates other translation factors. These include the eukaryotic initiation factor (eIF) 4E binding proteins (4E-BPs) and eukaryotic elongation factor 2 (eEF2). Insulin caused phosphorylation of 4E-BP1 and induced its dissociation from eIF4E, and these effects were also blocked by rapamycin. Concomitant with this, insulin increased the binding of eIF4E to eIF4G. Insulin also activated protein kinase B (PKB), which may lie upstream of p70 S6k and 4E-BP1, with the activation of the different isoforms being in the order α>β>γ. Insulin also caused inhibition of glycogen synthase kinase 3, which lies downstream of PKB, and of eEF2 kinase. The phosphorylation of eEF2 itself was also decreased by insulin, and this effect and the inactivation of eEF2 kinase were attenuated by rapamycin. The activation of overall protein synthesis by insulin in cardiomyocytes was substantially inhibited by rapamycin (but not by inhibitors of other specific signaling pathways, e.g., mitogen-activated protein kinase), showing that signaling events linked to mTOR play a major role in the control of translation by insulin in this cell type.

scholarly journals Band engineering and rational design of high-performance thermoelectric materials by first-principles

2016 ◽  
Vol 2 (2) ◽  
pp. 114-130 ◽  
Author(s):  
Lili Xi ◽  
Jiong Yang ◽  
Lihua Wu ◽  
Jihui Yang ◽  
Wenqing Zhang
Keyword(s):  
Thermoelectric Materials ◽  
First Principles ◽  
High Performance ◽  
Rational Design ◽  
Band Engineering

scholarly journals Structural Evolution, Redox Mechanism, and Ionic Diffusion in Rhombohedral Na2FeFe(CN)6 for Sodium-Ion Batteries: First-Principles Calculations

2022 ◽  
Author(s):  
Ya-Ping Wang ◽  
B. P. Hou ◽  
Xin-Rui Cao ◽  
Shunqing Wu ◽  
Zi-Zhong Zhu
Keyword(s):  
First Principles ◽  
Rational Design ◽  
Low Cost ◽  
Magnetic Moments ◽  
Three Dimensional ◽  
Structural Evolution ◽  
Sodium Ion ◽  
High Rate ◽  
Sodium Ion Batteries ◽  
First Principles Calculations

Abstract Prussian blue analogs (Na2FeFe(CN)6) have been regarded as potential cathode materials for sodium-ion batteries (SIBs) due to their low-cost iron resources and open framework. Herein, the detailed first-principles calculations have been performed to investigate the electrochemical properties of NaxFeFe(CN)6 during Na ion extraction. The material undergoes a phase transition from a dense rhombohedral to open cubic structure upon half-desodiation, which is resulted from competition of the Na−N Coulomb attraction and d−π covalent bonding of Fe−N. The analyses on the density of states, magnetic moments and Bader charges of NaxFeFe(CN)6 reveal that there involve in the successive redox reactions of high-spin Fe2+/Fe3+ and low-spin Fe2+/Fe3+ couples during desodiation. Moreover, the facile three-dimensional diffusion channels for Na+ ions exhibit low diffusion barriers of 0.4 eV ~ 0.44 eV, which ensures a rapid Na+ transport in the NaxFeFe(CN)6 framework, contributing to high rate performance of the battery. This study gives a deeper understanding of the electrochemical mechanisms of NaxFeFe(CN)6 during Na+ extraction, which is beneficial for the rational design of superior PBA cathodes for SIBs.

Rational design of bifunctional ORR/OER catalysts based on Pt/Pd-doped Nb2CT2 MXene by first-principles calculations

2020 ◽  
Vol 8 (6) ◽  
pp. 3097-3108 ◽  
Author(s):  
Dongxiao Kan ◽  
Dashuai Wang ◽  
Xilin Zhang ◽  
Ruqian Lian ◽  
Jing Xu ◽  
...  
Keyword(s):  
First Principles ◽  
Rational Design ◽  
Bifunctional Catalyst ◽  
First Principles Calculations

Nb2CF2–VF–Pt is confirmed to be the best bifunctional catalyst toward ORR and OER, with relative low theoretical overpotentials (0.40 V for ORR and 0.37 V for OER).

scholarly journals Regulation of translation by one-carbon metabolism in bacteria and the eukaryotic organelles

2020 ◽  
pp. jbc.REV120.011985
Author(s):  
Sunil Shetty ◽  
Umesh Varshney
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Carbon Metabolism ◽  
Mrna Translation ◽  
Energy Reserves ◽  
Cellular Activity ◽  
Translation Factors ◽  
Translation Apparatus ◽  
Alternative Translation ◽  
One Carbon Metabolism

Protein synthesis is an energetically costly cellular activity. It is therefore important that the process of mRNA translation remains in excellent synchrony with cellular metabolism and its energy reserves. Unregulated translation could lead to the production of incomplete, mistranslated, or misfolded proteins, squandering the energy needed for cellular sustenance, and causing cytotoxicity. One-carbon metabolism (OCM), an integral part of cellular intermediary metabolism, produces a number of one-carbon unit intermediates (formyl, methylene, methenyl, methyl). These OCM intermediates are required for the production of amino acids like methionine, and biomolecules such as purines, thymidylate, and redox regulators. In this review, we discuss how OCM impacts the translation apparatus (composed of ribosome, tRNA, mRNA, and translation factors) and regulates crucial steps in protein synthesis. More specifically, we address how the OCM metabolites regulate the fidelity and rate of translation initiation in bacteria and eukaryotic organelles such as mitochondria. Modulation of the fidelity of translation initiation by OCM opens new avenues to understand alternative translation mechanisms involved in stress tolerance and drug resistance.

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