6aax: Difference between revisions
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<StructureSection load='6aax' size='340' side='right'caption='[[6aax]], [[Resolution|resolution]] 2.99Å' scene=''> | <StructureSection load='6aax' size='340' side='right'caption='[[6aax]], [[Resolution|resolution]] 2.99Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6aax]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6aax]] is a 4 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=6AAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AAX FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.994Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6aax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aax OCA], [https://pdbe.org/6aax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aax RCSB], [https://www.ebi.ac.uk/pdbsum/6aax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aax ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/TFB1M_HUMAN TFB1M_HUMAN] Mitochondrial non-syndromic sensorineural deafness. Variations in TFB1M may influence the clinical expression of aminoglycoside-induced deafness caused by the A1555G mutation in the mitochondrial 12S rRNA. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/TFB1M_HUMAN TFB1M_HUMAN] S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity.<ref>PMID:11809803</ref> <ref>PMID:12068295</ref> <ref>PMID:12897151</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6aax" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6aax" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Adenosine dimethyltransferase 3D structures|Adenosine dimethyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gong | [[Category: Gong Q]] | ||
[[Category: Li | [[Category: Li F]] | ||
[[Category: Liu | [[Category: Liu X]] | ||
[[Category: Shen | [[Category: Shen S]] | ||
[[Category: Shi | [[Category: Shi Y]] | ||
[[Category: Wu | [[Category: Wu J]] | ||
[[Category: Wu | [[Category: Wu P]] | ||
[[Category: Zhang | [[Category: Zhang H]] | ||
Latest revision as of 12:23, 22 November 2023
Crystal structure of TFB1M and h45 with SAM in homo sapiensCrystal structure of TFB1M and h45 with SAM in homo sapiens
Structural highlights
DiseaseTFB1M_HUMAN Mitochondrial non-syndromic sensorineural deafness. Variations in TFB1M may influence the clinical expression of aminoglycoside-induced deafness caused by the A1555G mutation in the mitochondrial 12S rRNA. FunctionTFB1M_HUMAN S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity.[1] [2] [3] Publication Abstract from PubMedMitochondria are essential molecular machinery for the maintenance of cellular energy supply by the oxidative phosphorylation system (OXPHOS). Mitochondrial transcription factor B1 (TFB1M) is a dimethyltransferase that maintains mitochondrial homeostasis by catalyzing dimethylation of two adjacent adenines located in helix45 (h45) of 12S rRNA. This m62A modification is indispensable for the assembly and maturation of human mitochondrial ribosomes. However, both the mechanism of TFB1M catalysis and the precise function of TFB1M in mitochondrial homeostasis are unknown. Here we report the crystal structures of a ternary complex of human (hs) TFB1M-h45-S-adenosyl-methionine and a binary complex hsTFB1M-h45. The structures revealed a distinct mode of hsTFB1M interaction with its rRNA substrate and with the initial enzymatic state involved in m62A modification. The suppression of hsTFB1M protein level or the overexpression of inactive hsTFB1M mutants resulted in decreased ATP production and reduced expression of components of the mitochondrial OXPHOS without affecting transcription of the corresponding genes and their localization to the mitochondria. Therefore, hsTFB1M regulated the translation of mitochondrial genes rather than their transcription via m62A modification in h45. Structural insights into dimethylation of 12S rRNA by TFB1M: indispensable role in translation of mitochondrial genes and mitochondrial function.,Liu X, Shen S, Wu P, Li F, Liu X, Wang C, Gong Q, Wu J, Yao X, Zhang H, Shi Y Nucleic Acids Res. 2019 Aug 22;47(14):7648-7665. doi: 10.1093/nar/gkz505. PMID:31251801[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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