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'''Unreleased structure'''


The entry 6ajk is ON HOLD  until Paper Publication
==Crystal structure of TFB1M and h45 in homo sapiens==
<StructureSection load='6ajk' size='340' side='right'caption='[[6ajk]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ajk]] 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=6AJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AJK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.001&#8491;</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=6ajk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ajk OCA], [https://pdbe.org/6ajk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ajk RCSB], [https://www.ebi.ac.uk/pdbsum/6ajk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ajk ProSAT]</span></td></tr>
</table>
== 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 ==
[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;">
== Publication Abstract from PubMed ==
Mitochondria 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.


Authors: Liu, X., Shen, S., Wu, P., Li, F., Wang, C., Gong, Q., Wu, J., Zhang, H., Shi, Y.
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<ref>PMID:31251801</ref>


Description: Crystal structure of TFB1M and h45 in homo sapiens
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Wu, J]]
<div class="pdbe-citations 6ajk" style="background-color:#fffaf0;"></div>
[[Category: Zhang, H]]
 
[[Category: Liu, X]]
==See Also==
[[Category: Gong, Q]]
*[[Adenosine dimethyltransferase 3D structures|Adenosine dimethyltransferase 3D structures]]
[[Category: Wang, C]]
== References ==
[[Category: Wu, P]]
<references/>
[[Category: Shen, S]]
__TOC__
[[Category: Li, F]]
</StructureSection>
[[Category: Shi, Y]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gong Q]]
[[Category: Li F]]
[[Category: Liu X]]
[[Category: Shen S]]
[[Category: Shi Y]]
[[Category: Wang C]]
[[Category: Wu J]]
[[Category: Wu P]]
[[Category: Zhang H]]

Latest revision as of 12:32, 22 November 2023

Crystal structure of TFB1M and h45 in homo sapiensCrystal structure of TFB1M and h45 in homo sapiens

Structural highlights

6ajk 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 3.001Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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.[1] [2] [3]

Publication Abstract from PubMed

Mitochondria 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 Also

References

  1. ↑ McCulloch V, Seidel-Rogol BL, Shadel GS. A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine. Mol Cell Biol. 2002 Feb;22(4):1116-25. PMID:11809803
  2. ↑ Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM. Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet. 2002 Jul;31(3):289-94. Epub 2002 Jun 17. PMID:12068295 doi:http://dx.doi.org/10.1038/ng909
  3. ↑ McCulloch V, Shadel GS. Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity. Mol Cell Biol. 2003 Aug;23(16):5816-24. PMID:12897151
  4. ↑ Liu X, Shen S, Wu P, Li F, Liu X, Wang C, Gong Q, Wu J, Yao X, Zhang H, Shi Y. Structural insights into dimethylation of 12S rRNA by TFB1M: indispensable role in translation of mitochondrial genes and mitochondrial function. Nucleic Acids Res. 2019 Aug 22;47(14):7648-7665. doi: 10.1093/nar/gkz505. PMID:31251801 doi:http://dx.doi.org/10.1093/nar/gkz505

6ajk, resolution 3.00Å

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