An archaeal aminoacyl-tRNA synthetase complex for improved substrate quality control

Crnković, Ana; Čavužić, Mirela; Godinić-Mikulčić, Vlatka; Anderluh, Gregor; Weygand-Đurašević, Ivana; Gruić-Sovulj, Ita

doi:10.1016/j.biochi.2017.12.006

Cited by 4 publications

(4 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interaction of yeast SerRS with peroxisomal protein Pex21p enhances cognate tRNA binding and moderately stimulates the aminoacylation efficiency of SerRS . SerRS and arginyl‐tRNA synthetase (ArgRS) from methanogenic archaea Methanothermobacter thermautotrophicus form a complex that enhances the SerRS aminoacylation activity under extreme conditions and suppresses aminoacylation of naïve, unmodified tRNA Arg by ArgRS, likely improving translational accuracy . In addition, the SerRS:ArgRS complex interacts with ribosomal proteins in the L7/L12 stalk region of the ribosome, suggesting a mechanism of tRNA recycling .…”

Section: Introductionmentioning

confidence: 99%

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase

et al. 2019

Self Cite

View full text Add to dashboard Cite

The rules of the genetic code are established by aminoacyl‐tRNA synthetases (aaRSs) enzymes, which covalently link tRNA with the cognate amino acid. Many aaRSs are involved in diverse cellular processes beyond translation, acting alone, or in complex with other proteins. However, studies of aaRS noncanonical assembly and functions in plants are scarce, as are structural studies of plant aaRSs. Here, we have solved the crystal structure of Arabidopsis thaliana cytosolic seryl‐tRNA synthetase (SerRS), which is the first crystallographic structure of a plant aaRS. Arabidopsis SerRS displays structural features typical of canonical SerRSs, except for a unique intrasubunit disulfide bridge. In a yeast two‐hybrid screen, we identified BEN1, a protein involved in the metabolism of plant brassinosteroid hormones, as a protein interactor of Arabidopsis SerRS. The SerRS:BEN1 complex is one of the first protein complexes of plant aaRSs discovered so far, and is a rare example of an aaRS interacting with an enzyme involved in primary or secondary metabolism. To pinpoint regions responsible for this interaction, we created truncated variants of SerRS and BEN1, and identified that the interaction interface involves the SerRS globular catalytic domain and the N‐terminal extension of BEN1 protein. BEN1 does not have a strong impact on SerRS aminoacylation activity, indicating that the primary function of the complex is not the modification of SerRS canonical activity. Perhaps SerRS performs as yet unknown noncanonical functions mediated by BEN1. These findings indicate that – via SerRS and BEN1 – a link exists between the protein translation and steroid metabolic pathways of the plant cell. Database Structural data are available in the PDB under the accession number PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6GIR.

show abstract

Section: Introductionmentioning

confidence: 99%

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…It was shown that SerRS interacted with arginyl-tRNA-synthetase (ArgRS) (Figure 3C) [119]. The SerRS:ArgRS complex suppressed the aminoacylation of naive, unmodified tRNA Arg by ArgRS, likely improving translational accuracy [121]. Robust ArgRS:SerRS interaction promoted serylation and enhanced SerRS:tRNA Ser complex formation at elevated temperature and osmolarity, indicating a role in the thermo-and osmoadaptation mechanisms of thermophilic methanogenic archaea [119].…”

Section: Interactions Of Atypical Serrs With Argrs and Ribosomal Prot...mentioning

confidence: 99%

“…Several SerRS complexes appear important for the fine-tuning of translation. The complex between M. thermautotrophicus SerRS and ArgRS promotes serylation reactions at extreme environmental conditions [119] and suppresses aminoacylation of unmodified tRNA Arg [121]. The interplay of both aaRSs with the ribosomal P-stalk likely promotes tRNA channeling, enabling direct aa-tRNA transfer from aaRS to elongation factor to ribosome without dissociation into the cellular fluid [122].…”

Section: Conclusion 81 Protein-protein Interaction Network Of Serrssmentioning

confidence: 99%

Protein–Protein Interactions of Seryl-tRNA Synthetases with Emphasis on Human Counterparts and Their Connection to Health and Disease

Dulic,

Godinic-Mikulcic,

Kekez

et al. 2024

Life

View full text Add to dashboard Cite

Seryl-tRNA synthetases (SerRSs), members of the aminoacyl-tRNA synthetase family, interact with diverse proteins, enabling SerRSs to enhance their role in the translation of the genetic message or to perform alternative functions in cellular processes beyond translation. Atypical archaeal SerRS interacts with arginyl-tRNA synthetase and proteins of the ribosomal P-stalk to optimize translation through tRNA channeling. The complex between yeast SerRS and peroxin Pex21p provides a connection between translation and peroxisome function. The partnership between Arabidopsis SerRS and BEN1 indicates a link between translation and brassinosteroid metabolism and may be relevant in plant stress response mechanisms. In Drosophila, the unusual heterodimeric mitochondrial SerRS coordinates mitochondrial translation and replication via interaction with LON protease. Evolutionarily conserved interactions of yeast and human SerRSs with m3C32 tRNA methyltransferases indicate coordination between tRNA modification and aminoacylation in the cytosol and mitochondria. Human cytosolic SerRS is a cellular hub protein connecting translation to vascular development, angiogenesis, lipogenesis, and telomere maintenance. When translocated to the nucleus, SerRS acts as a master negative regulator of VEGFA gene expression. SerRS alone or in complex with YY1 and SIRT2 competes with activating transcription factors NFκB1 and c-Myc, resulting in balanced VEGFA expression important for proper vascular development and angiogenesis. In hypoxia, SerRS phosphorylation diminishes its binding to the VEGFA promoter, while the lack of nutrients triggers SerRS glycosylation, reducing its nuclear localization. Additionally, SerRS binds telomeric DNA and cooperates with the shelterin protein POT1 to regulate telomere length and cellular senescence. As an antitumor and antiangiogenic factor, human cytosolic SerRS appears to be a promising drug target and therapeutic agent for treating cancer, cardiovascular diseases, and possibly obesity and aging.

show abstract

“…The continuous weighting framework in Section 4.2 builds on the seminal paper of Diebold et al (1998). It is close in spirit to the approach of Crnkovic and Drachman (1996), who apply a statistic based on a weighted Kuiper distance between the distribution of PIT values and the uniform, and subsumes the likelihood ratio test of Berkowitz (2001) based on fitting a truncated normal distribution to probit-transformed PIT-values. Most closely related to our work, Du and Escanciano (2017) and Costanzino and Curran (2015) have proposed test statistics for spectral risk measures which can be viewed as special cases of our univariate spectral Z-test.…”

Section: Tests Of Unconditional Coveragementioning

confidence: 99%

Spectral Backtests of Forecast Distributions with Application to Risk Management

Gordy

McNeil²

2018

FEDS

View full text Add to dashboard Cite

We study a class of backtests for forecast distributions in which the test statistic depends on a spectral transformation that weights exceedance events by a function of the modeled probability level. The weighting scheme is specified by a kernel measure which makes explicit the user's priorities for model performance. The class of spectral backtests includes tests of unconditional coverage and tests of conditional coverage. We show how the class embeds a wide variety of backtests in the existing literature, and further propose novel variants which are easily implemented, well-sized and have good power. In an empirical application, we backtest forecast distributions for the overnight P&L of ten bank trading portfolios. For some portfolios, test results depend materially on the choice of kernel.

show abstract

An archaeal aminoacyl-tRNA synthetase complex for improved substrate quality control

Cited by 4 publications

References 49 publications

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase

Protein–Protein Interactions of Seryl-tRNA Synthetases with Emphasis on Human Counterparts and Their Connection to Health and Disease

Spectral Backtests of Forecast Distributions with Application to Risk Management

Contact Info

Product

Resources

About