5l6d
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the human METTL3-METTL14 complex bound to SAH== | |
| + | <StructureSection load='5l6d' size='340' side='right'caption='[[5l6d]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5l6d]] 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=5L6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L6D 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]] 1.852Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></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=5l6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6d OCA], [https://pdbe.org/5l6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l6d RCSB], [https://www.ebi.ac.uk/pdbsum/5l6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l6d ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MTA70_HUMAN MTA70_HUMAN] N6-methyltransferase that methylates adenosine residues of some RNAs and acts as a regulator of the circadian clock, differentiation of embryonic stem cells and primary miRNA processing. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in the efficiency of mRNA splicing, processing, translation efficiency, editing and mRNA stability (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:9409616). M6A regulates the length of the circadian clock: acts as a early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A also acts as a regulator of mRNA stability: in embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). Mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998).[UniProtKB:Q8C3P7]<ref>PMID:22575960</ref> <ref>PMID:24284625</ref> <ref>PMID:25719671</ref> <ref>PMID:25799998</ref> <ref>PMID:26321680</ref> <ref>PMID:26593424</ref> <ref>PMID:9409616</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Methylation of adenosines at the N(6) position (m(6)A) is a dynamic and abundant epitranscriptomic mark that regulates critical aspects of eukaryotic RNA metabolism in numerous biological processes. The RNA methyltransferases METTL3 and METTL14 are components of a multisubunit m(6)A writer complex whose enzymatic activity is substantially higher than the activities of METTL3 or METTL14 alone. The molecular mechanism underpinning this synergistic effect is poorly understood. Here we report the crystal structure of the catalytic core of the human m(6)A writer complex comprising METTL3 and METTL14. The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. These studies illuminate the molecular mechanism and evolutionary history of eukaryotic m(6)A modification in post-transcriptional genome regulation. | ||
| - | + | Structural insights into the molecular mechanism of the m(6)A writer complex.,Sledz P, Jinek M Elife. 2016 Sep 14;5. pii: e18434. doi: 10.7554/eLife.18434. PMID:27627798<ref>PMID:27627798</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Jinek | + | <div class="pdbe-citations 5l6d" style="background-color:#fffaf0;"></div> |
| - | [[Category: Sledz | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Jinek M]] | ||
| + | [[Category: Sledz P]] | ||
Current revision
Crystal structure of the human METTL3-METTL14 complex bound to SAH
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