6W6C

Structural and catalytic roles of human 18S rRNA methyltransferases DIMT1 in ribosome assembly and translation

6W6C の概要

• エントリーDOI: 10.2210/pdb6w6c/pdb
• 分子名称: Probable dimethyladenosine transferase (2 entities in total)
• 機能のキーワード: rna modification enzyme, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70584.87

構造登録者

Shen, H.,Stoute, J. (登録日: 2020-03-16, 公開日: 2020-07-08, 最終更新日: 2023-10-18)

主引用文献

Shen, H.,Stoute, J.,Liu, K.F.
Structural and catalytic roles of the human 18SrRNA methyltransferases DIMT1 in ribosome assembly and translation.
J.Biol.Chem., 295:12058-12070, 2020

PubMed Abstract: rRNA-modifying enzymes participate in ribosome assembly. However, whether the catalytic activities of these enzymes are important for the ribosome assembly and other cellular processes is not fully understood. Here, we report the crystal structure of WT human dimethyladenosine transferase 1 (DIMT1), an 18 rRNA -dimethyladenosine (mA) methyltransferase, and results obtained with a catalytically inactive DIMT1 variant. We found that heterozygous HEK 293T cells have a significantly decreased 40S fraction and reduced protein synthesis but no major changes in mA levels in 18 rRNA. Expression of a catalytically inactive variant, DIMT1-E85A, in WT and cells significantly decreased mA levels in 18S rRNA, indicating a dominant-negative effect of this variant on mA levels. However, expression of the DIMT1-E85A variant restored the defects in 40S levels. Of note, unlike WT DIMT1, DIMT1-E85A could not revert the defects in protein translation. We found that the differences between this variant and the WT enzyme extended to translation fidelity and gene expression patterns in DNA damage response pathways. These results suggest that the catalytic activity of DIMT1 is involved in protein translation and that the overall protein scaffold of DIMT1, regardless of the catalytic activity on mA in 18 rRNA, is essential for 40S assembly.

PubMed: 32616653
DOI: 10.1074/jbc.RA120.014236

実験手法

X-RAY DIFFRACTION (2.38 Å)