6du5
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of hMettl16 catalytic domain in complex with MAT2A 3'UTR hairpin 6== | |
| + | <StructureSection load='6du5' size='340' side='right'caption='[[6du5]], [[Resolution|resolution]] 3.01Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6du5]] 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=6DU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DU5 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]] 3.006Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6du5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6du5 OCA], [https://pdbe.org/6du5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6du5 RCSB], [https://www.ebi.ac.uk/pdbsum/6du5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6du5 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MET16_HUMAN MET16_HUMAN] RNA N6-methyltransferase that methylates adenosine residues of a subset of RNAs and plays a key role in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753). In presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A expression (PubMed:28525753). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200). Also able to bind various lncRNAs (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311).<ref>PMID:27872311</ref> <ref>PMID:28525753</ref> <ref>PMID:29051200</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | S-adenosylmethionine (SAM) is an essential metabolite that acts as a cofactor for most methylation events in the cell. The N(6)-methyladenosine (m(6)A) methyltransferase METTL16 controls SAM homeostasis by regulating the abundance of SAM synthetase MAT2A mRNA in response to changing intracellular SAM levels. Here we present crystal structures of METTL16 in complex with MAT2A RNA hairpins to uncover critical molecular mechanisms underlying the regulated activity of METTL16. The METTL16-RNA complex structures reveal atomic details of RNA substrates that drive productive methylation by METTL16. In addition, we identify a polypeptide loop in METTL16 near the SAM binding site with an autoregulatory role. We show that mutations that enhance or repress METTL16 activity in vitro correlate with changes in MAT2A mRNA levels in cells. Thus, we demonstrate the structural basis for the specific activity of METTL16 and further suggest the molecular mechanisms by which METTL16 efficiency is tuned to regulate SAM homeostasis. | ||
| - | + | Structural Basis for Regulation of METTL16, an S-Adenosylmethionine Homeostasis Factor.,Doxtader KA, Wang P, Scarborough AM, Seo D, Conrad NK, Nam Y Mol Cell. 2018 Sep 20;71(6):1001-1011.e4. doi: 10.1016/j.molcel.2018.07.025. Epub, 2018 Sep 6. PMID:30197297<ref>PMID:30197297</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6du5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Doxtader K]] | ||
| + | [[Category: Nam Y]] | ||
| + | [[Category: Wang P]] | ||
Current revision
Crystal structure of hMettl16 catalytic domain in complex with MAT2A 3'UTR hairpin 6
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