| 1990 |
ATE1 encodes arginyl-tRNA-protein transferase (R-transferase) that catalyzes post-translational conjugation of Arg to N-terminal residues of acceptor proteins; expression of yeast ATE1 in E. coli (which lacks R-transferases) conferred Arg-transferase activity, and null ate1 mutants lack this activity and cannot degrade N-end rule substrates requiring Arg-transferase action. |
Heterologous expression in E. coli, null mutant analysis, in vitro enzymatic assay |
The Journal of biological chemistry |
High |
2185248
|
| 2014 |
ATE1 catalyzes arginylation not only at N-terminal alpha-amino groups but also at internal side-chain carboxylates of Asp and Glu residues within intact proteins in vivo, revealing an unconventional midchain arginylation mechanism. |
Mass spectrometry (in vivo arginylation profiling), in vitro ATE1 arginylation assay with purified components |
Chemistry & biology |
High |
24529990
|
| 2022 |
Crystal structure of K. lactis Ate1 R-transferase at 58 kDa reveals two domains that together recognize an acidic N-terminal residue of the acceptor substrate, the Arg residue of Arg-tRNAArg, and the 3'-proximal tRNAArg segment; the active site is located between the two domains. Hemin (Fe3+-heme) inhibits Nt-arginylation activity and induces disulfide-mediated oligomerization of Ate1. Site-directed mutagenesis guided by the structure identified specific binding residues. |
X-ray crystallography, site-directed mutagenesis, in vitro and in vivo arginylation assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
35878037
|
| 2022 |
Crystal structure of S. cerevisiae ATE1 (ScATE1) in apo form reveals a bilobed protein with a GCN5-related N-acetyltransferase (GNAT) fold; the domain-domain interface constitutes the catalytic active site and tRNA-binding region. The N-terminal domain that binds a regulatory [Fe-S] cluster is dynamic and disordered in the absence of metal, indicating regulatory influence of this region. |
X-ray crystallography, SEC-SAXS, cryo-EM 2D class averaging, structural superposition |
Journal of molecular biology |
High |
36087779
|
| 2025 |
Cryo-EM structure of human ATE1 in complex with Arg-tRNAArg and an N-terminal Asp peptide shows two adjacent pockets binding the Nt-substrate and Arg-tRNAArg respectively, the tRNA being wrapped by a long unstructured loop. In the apo state, two ATE1 monomers form a homodimer. Substrate selectivity is achieved through multivalent interactions with Kd values in the micromolar range. |
Cryo-EM structure determination, binding affinity measurements |
Autophagy |
High |
40099869
|
| 2016 |
ATE1/arginylation promotes cell death and/or growth arrest in response to oxidative, heat, osmotic, heavy metal, and radiation stresses; ATE1 protein levels rise under acute stress, and the elevated ATE1 directly promotes cell death in an arginylation-activity-dependent manner. ATE1 is also required to suppress mutation frequency under DNA-damaging conditions. |
ATE1 knockout/knockdown in yeast, mouse, and human cells; genetic complementation with catalytically inactive ATE1; functional cell death and mutagenesis assays |
Cell death & disease |
Medium |
27685622
|
| 2017 |
ATE1 localizes prominently to neuronal growth cones via zipcode-mediated mRNA targeting; Ate1 mRNA co-localizes with arginylated β-actin at growth cone tips, and co-translational arginylation of β-actin at growth cones drives growth cone migration and neurite outgrowth. Conditional Ate1 knockout in the nervous system causes defects in neuronal migration, reduced neurite outgrowth, and decreased doublecortin and F-actin in growth cones. |
Conditional mouse knockout (Nestin-Cre), live-cell imaging, FISH, fluorescence microscopy, protein synthesis inhibitor experiments |
Developmental biology |
Medium |
28844905
|
| 2013 |
ATE1 directly interacts with myosin II in platelets (co-immunoprecipitation); platelet-specific ATE1 knockout leads to enhanced myosin regulatory light chain phosphorylation at Ser19, enhanced clot retraction, and increased in vivo thrombus formation, indicating arginylation modulates myosin contractility. |
Conditional platelet/megakaryocyte-specific knockout mouse, co-immunoprecipitation, phosphorylation analysis, in vivo thrombosis assay |
Haematologica |
Medium |
24293517
|
| 2018 |
In Dictyostelium discoideum, Ate1 knockout abolishes focal actin adhesion sites and reduces adhesion; mass spectrometry identified four arginylation sites in the major actin isoform plus sites in actin-binding proteins. Actin from ate1-null cells has diminished polymerization capacity in vitro. Ate1-GFP rapidly relocalizes to sites of newly formed actin-rich protrusions. |
Gene knockout, live-cell microscopy, mass spectrometry, in vitro actin polymerization assay, chemotaxis assay |
Molecular biology of the cell |
Medium |
30586322
|
| 2021 |
Ate1 regulates RGS7 protein levels by facilitating its proteasomal degradation; conditional Ate1 knockout in the nervous system elevates RGS7 levels in retinal ON bipolar cells, increases light-evoked ON-bipolar response sensitivities, and in cultured MEFs, RGS7 degradation by the proteasome is abolished in Ate1 knockout cells. |
Conditional mouse knockout (nervous system), electroretinography, proteasome inhibitor experiments in MEF cells |
Scientific reports |
Medium |
33931669
|
| 2021 |
ATE1 splicing is controlled by competing RNA secondary structures: five conserved intronic elements (R1–R5) regulate mutual exclusion of exons 7a and 7b, with R1 and R4 competing for base-pairing with R3, and an ultra-long-range R2–R5 interaction spanning 30 kb. Disruption of these RNA structures by mutation or LNA/DNA mixmers abolishes mutually exclusive exon splicing, and co-transcriptional folding links exon 7a inclusion to RNA Pol II elongation rate. |
Minigene splicing assay with single/double/compensatory mutations, LNA/DNA mixmer blocking, endogenous pre-mRNA analysis |
Nucleic acids research |
High |
33330934
|
| 2020 |
Liat1 (Ligand of Ate1) physically interacts with Ate1 and undergoes liquid-liquid phase separation in the nucleolus via an intrinsically disordered N-terminal region; Jmjd6 lysyl-hydroxylase modifies Liat1's poly-K region and inhibits its nucleolar targeting. |
Bimolecular fluorescence complementation, immunocytochemistry, IDR characterization, phase separation assay |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
33443146
|
| 2023 |
ATE1 binds a regulatory iron-sulfur ([Fe-S]) cluster in its N-terminal domain that functions as an oxygen sensor to regulate ATE1 activity; chemical reconstitution under anoxic conditions restores [Fe-S] cluster binding in both yeast and mouse ATE1. |
Anaerobic [Fe-S] cluster reconstitution, spectroscopic characterization |
Methods in molecular biology |
Medium |
37010764
|
| 2024 |
Mouse ATE1 contains an intrinsically disordered region (IDR) absent in yeast ATE1; HDX-MS and SAXS demonstrate this IDR is present in all mouse ATE1 splice variants and is predicted to facilitate complex formation with tRNAArg. |
SEC, SAXS, HDX-MS, AlphaFold modeling, bioinformatics |
Biochemistry |
Medium |
39642180
|
| 2024 |
tRNAArg directly binds in vitro to TDP-43 RNA recognition motifs and stabilizes binding via TDP-43 dimerization (promoted by the N-terminal domain and NLS); the arginylation cofactor LIAT1 also binds tRNAArg in vitro, identifying LIAT1 as an RNA-binding protein. |
In vitro binding assays with recombinant proteins and in vitro-transcribed tRNA |
microPublication biology |
Low |
39081859
|
| 2021 |
ATE1 inhibits liver cancer growth by facilitating proteasomal degradation of RGS5, which in turn maintains GSK3-β activity and promotes β-catenin degradation, thereby suppressing Wnt/β-catenin signaling; loss- and gain-of-function assays with RGS5 and GSK3-β inhibitor confirmed RGS5 as a key effector downstream of ATE1. |
Lentivirus-mediated knockdown/overexpression, loss- and gain-of-function, GSK3-β inhibitor rescue experiments, in vitro and in vivo tumor assays |
Molecular cancer research |
Medium |
34158395
|
| 2024 |
Mitochondrial translocation of Ate1 is promoted by oxidative stressors and is essential for inducing apoptotic cell death; Ate1-induced cell death depends on mitochondrial permeability pore formation and apoptosis-inducing factor, but not on electron transport chain activity or ROS, and is independent of cytosolic ubiquitin-proteasome, autophagy, or ER stress pathways. |
Yeast genetic and cell biology experiments, mitochondrial fractionation, mitochondrial permeability pore assays, AIF analysis |
bioRxivpreprint |
Medium |
bio_10.1101_2024.11.22.624728
|