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5yz9

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Revision as of 06:56, 27 March 2019

zinc finger domain of METTL3-METTL14 N6-methyladenosine methyltransferase

Structural highlights

5yz9 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	METTL3, MTA70 (HUMAN)
Activity:	mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase, with EC number 2.1.1.62
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

N(6)-methyladenosine (m(6)A), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3' consensus sequence, but does not to one without. The ZFD thus serves as the target recognition domain, a structural feature previously shown for DNA methyltransferases, and cooperates with the MTDs of METTL3-METTL14 for catalysis. However, the interaction between the ZFD and the specific RNA is extremely weak, with the binding affinity at several hundred micromolar under physiological conditions. The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel beta-sheet. Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface. As a division of labor, the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from beta-sheet and zinc finger 2. Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded, which may permit the cooperation between the two domains during catalysis. Together, the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m(6)A modification.

Solution structure of the RNA recognition domain of METTL3-METTL14 N(6)-methyladenosine methyltransferase.,Huang J, Dong X, Gong Z, Qin LY, Yang S, Zhu YL, Wang X, Zhang D, Zou T, Yin P, Tang C Protein Cell. 2018 Mar 14. pii: 10.1007/s13238-018-0518-7. doi:, 10.1007/s13238-018-0518-7. PMID:29542011^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, Cesarkas K, Jacob-Hirsch J, Amariglio N, Kupiec M, Sorek R, Rechavi G. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012 Apr 29;485(7397):201-6. doi: 10.1038/nature11112. PMID:22575960 doi:http://dx.doi.org/10.1038/nature11112
↑ Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, Ren B, Pan T, He C. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014 Jan 2;505(7481):117-20. doi: 10.1038/nature12730. Epub 2013 Nov 27. PMID:24284625 doi:http://dx.doi.org/10.1038/nature12730
↑ Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 2015 Feb 26;518(7540):560-4. doi: 10.1038/nature14234. PMID:25719671 doi:http://dx.doi.org/10.1038/nature14234
↑ Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015 Mar 26;519(7544):482-5. doi: 10.1038/nature14281. Epub 2015 Mar 18. PMID:25799998 doi:http://dx.doi.org/10.1038/nature14281
↑ Alarcon CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF. HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events. Cell. 2015 Sep 10;162(6):1299-308. doi: 10.1016/j.cell.2015.08.011. Epub 2015 Aug, 27. PMID:26321680 doi:http://dx.doi.org/10.1016/j.cell.2015.08.011
↑ Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian SB, Jaffrey SR. 5' UTR m(6)A Promotes Cap-Independent Translation. Cell. 2015 Nov 5;163(4):999-1010. doi: 10.1016/j.cell.2015.10.012. Epub 2015 Oct , 22. PMID:26593424 doi:http://dx.doi.org/10.1016/j.cell.2015.10.012
↑ Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. 1997 Nov;3(11):1233-47. PMID:9409616
↑ Huang J, Dong X, Gong Z, Qin LY, Yang S, Zhu YL, Wang X, Zhang D, Zou T, Yin P, Tang C. Solution structure of the RNA recognition domain of METTL3-METTL14 N(6)-methyladenosine methyltransferase. Protein Cell. 2018 Mar 14. pii: 10.1007/s13238-018-0518-7. doi:, 10.1007/s13238-018-0518-7. PMID:29542011 doi:http://dx.doi.org/10.1007/s13238-018-0518-7

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5yz9"

@@ Line 1: / Line 1: @@
 ==zinc finger domain of METTL3-METTL14 N6-methyladenosine methyltransferase==
-<StructureSection load='5yz9' size='340' side='right' caption='[[5yz9]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
+<StructureSection load='5yz9' size='340' side='right'caption='[[5yz9]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5yz9]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YZ9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5yz9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YZ9 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METTL3, MTA70 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/mRNA_(2'-O-methyladenosine-N(6)-)-methyltransferase mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.62 2.1.1.62] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5yz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yz9 OCA], [http://pdbe.org/5yz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yz9 RCSB], [http://www.ebi.ac.uk/pdbsum/5yz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yz9 ProSAT]</span></td></tr>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Dong, X]]
 [[Category: Gong, Z]]

5yz9

From Proteopedia

Revision as of 06:56, 27 March 2019

zinc finger domain of METTL3-METTL14 N6-methyladenosine methyltransferase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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