EMD-17531

Single-particle
3.8 Å
EMD-17531 Deposition: 30/05/2023
Map released: 12/06/2024
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-17531

SerRS bound to serine tRNA

EMD-17531

Single-particle
3.8 Å
EMD-17531 Deposition: 30/05/2023
Map released: 12/06/2024
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Trichoplusia ni
Sample: METTL6 tRNA SerRS complex in a 1:2:2 stoichiometry
Raw data: EMPIAR-11578

Deposition Authors: Throll P , Dolce LG , Kowalinski E
Structural basis of tRNA recognition by the m 3 C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase.
Throll P , G Dolce L , Rico-Lastres P, Arnold K , Tengo L , Basu S , Kaiser S, Schneider R, Kowalinski E
(2024) Nat Struct Mol Biol , 31 , 1614 - 1624
PUBMED: 38918637
DOI: doi:10.1038/s41594-024-01341-3
ISSN: 1545-9985
Abstract:
Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (m3C) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification can cause aggressive cancers and metabolic disturbances. Here, we report the cryo-electron microscopy structure of the human m3C tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNASer. Through the complex structure, we identify the tRNA-binding domain of METTL6. We show that SerRS acts as the tRNASer substrate selection factor for METTL6. We demonstrate that SerRS augments the methylation activity of METTL6 and that direct contacts between METTL6 and SerRS are necessary for efficient tRNASer methylation. Finally, on the basis of the structure of METTL6 in complex with SerRS and tRNASer, we postulate a universal tRNA-binding mode for m3C RNA methyltransferases, including METTL2 and METTL8, suggesting that these mammalian paralogs use similar ways to engage their respective tRNA substrates and cofactors.