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| | <StructureSection load='6w6f' size='340' side='right'caption='[[6w6f]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='6w6f' size='340' side='right'caption='[[6w6f]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6w6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W6F OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W6F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6w6f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W6F FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6w6c|6w6c]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DIMT1, DIMT1L, HUSSY-05 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6w6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w6f OCA], [https://pdbe.org/6w6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w6f RCSB], [https://www.ebi.ac.uk/pdbsum/6w6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w6f ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/18S_rRNA_(adenine(1779)-N(6)/adenine(1780)-N(6))-dimethyltransferase 18S rRNA (adenine(1779)-N(6)/adenine(1780)-N(6))-dimethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.183 2.1.1.183] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w6f OCA], [http://pdbe.org/6w6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w6f RCSB], [http://www.ebi.ac.uk/pdbsum/6w6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w6f ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DIM1_HUMAN 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).<ref>PMID:25851604</ref> | + | [https://www.uniprot.org/uniprot/DIM1_HUMAN 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).<ref>PMID:25851604</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Shen, H]] | + | [[Category: Shen H]] |
| - | [[Category: Stoute, J]] | + | [[Category: Stoute J]] |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rna modification enzyme]]
| + | |
| Structural highlights
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).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zorbas C, Nicolas E, Wacheul L, Huvelle E, Heurgue-Hamard V, Lafontaine DL. The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis. Mol Biol Cell. 2015 Jun 1;26(11):2080-95. doi: 10.1091/mbc.E15-02-0073. Epub 2015, Apr 7. PMID:25851604 doi:http://dx.doi.org/10.1091/mbc.E15-02-0073
- ↑ Shen H, Stoute J, Liu KF. Structural and catalytic roles of the human 18S rRNA methyltransferases DIMT1 in ribosome assembly and translation. J Biol Chem. 2020 Aug 21;295(34):12058-12070. doi: 10.1074/jbc.RA120.014236. Epub, 2020 Jul 2. PMID:32616653 doi:http://dx.doi.org/10.1074/jbc.RA120.014236
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