6w6f

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

spinqualitylabelsall models 6w6f, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6w6f is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DIM1_HUMAN Specifically dimethylates two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA in the 40S particle (PubMed:25851604). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production independently of its RNA-modifying catalytic activity (PubMed:25851604). Publication Abstract from PubMed 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 18S rRNA N (6,6)-dimethyladenosine (m2 (6,6)A) methyltransferase, and results obtained with a catalytically inactive DIMT1 variant. We found that DIMT1 (+/-) heterozygous HEK 293T cells have a significantly decreased 40S fraction and reduced protein synthesis but no major changes in m2 (6,6)A levels in 18S rRNA. Expression of a catalytically inactive variant, DIMT1-E85A, in WT and DIMT1 (+/-) cells significantly decreased m2 (6,6)A levels in 18S rRNA, indicating a dominant-negative effect of this variant on m2 (6,6)A 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 m2 (6,6)A in 18S rRNA, is essential for 40S assembly. Structural and catalytic roles of the human 18S rRNA methyltransferases DIMT1 in ribosome assembly and translation.,Shen H, Stoute J, Liu KF J Biol Chem. 2020 Aug 21;295(34):12058-12070. doi: 10.1074/jbc.RA120.014236. Epub, 2020 Jul 2. PMID:32616653 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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