6rt6: Difference between revisions

Revision as of 13:07, 18 December 2019

The YTH domain of YTHDC1 protein in complex with GGm6AC oligonucleotide

Structural highlights

6rt6 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	SO4
NonStd Res:	6MZ
Gene:	YTHDC1, KIAA1966, YT521 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[YTDC1_HUMAN] RNA-binding protein that regulates alternative splice site selection.^[1]

Publication Abstract from PubMed

N6-methyladenosine (m(6)A) is the most prevalent chemical modification in human mRNAs. Its recognition by reader proteins enables many cellular functions, including splicing and translation of mRNAs. However, the binding mechanisms of m(6)A-containing RNAs to their readers are still elusive due to the unclear roles of m(6)A-flanking ribonucleotides. Here, we use a model system, YTHDC1 with its RNA motif 5'-G-2G-1(m(6)A)C+1U+2-3', to investigate the binding mechanisms by atomistic simulations, X-ray crystallography, and isothermal titration calorimetry. The experimental data and simulation results show that m(6)A is captured by an aromatic cage of YTHDC1 and the 3' terminus nucleotides are stabilized by cation-pi-pi interactions, while the 5' terminus remains flexible. Moreover, simulations of unbound RNA motifs reveal that the methyl group of m(6)A and the 5' terminus shift the conformational preferences of the oligoribonucleotides to the bound-like conformation, thereby facilitating the association process. The binding mechanisms may help in the discovery of chemical probes against m(6)A reader proteins.

Flexible binding of m(6)A reader protein YTHDC1 to its preferred RNA motif.,Li Y, Bedi RK, Wiedmer L, Huang D, Sledz P, Caflisch A J Chem Theory Comput. 2019 Oct 31. doi: 10.1021/acs.jctc.9b00987. PMID:31670957^[2]

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

References

↑ Zhang Z, Theler D, Kaminska KH, Hiller M, de la Grange P, Pudimat R, Rafalska I, Heinrich B, Bujnicki JM, Allain FH, Stamm S. The YTH domain is a novel RNA binding domain. J Biol Chem. 2010 May 7;285(19):14701-10. doi: 10.1074/jbc.M110.104711. Epub 2010, Feb 18. PMID:20167602 doi:https://dx.doi.org/10.1074/jbc.M110.104711
↑ Li Y, Bedi RK, Wiedmer L, Huang D, Sledz P, Caflisch A. Flexible binding of m(6)A reader protein YTHDC1 to its preferred RNA motif. J Chem Theory Comput. 2019 Oct 31. doi: 10.1021/acs.jctc.9b00987. PMID:31670957 doi:https://dx.doi.org/10.1021/acs.jctc.9b00987

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OCA

[1] Zhang Z, Theler D, Kaminska KH, Hiller M, de la Grange P, Pudimat R, Rafalska I, Heinrich B, Bujnicki JM, Allain FH, Stamm S. The YTH domain is a novel RNA binding domain. J Biol Chem. 2010 May 7;285(19):14701-10. doi: 10.1074/jbc.M110.104711. Epub 2010, Feb 18. PMID:20167602 doi:https://dx.doi.org/10.1074/jbc.M110.104711

[2] Li Y, Bedi RK, Wiedmer L, Huang D, Sledz P, Caflisch A. Flexible binding of m(6)A reader protein YTHDC1 to its preferred RNA motif. J Chem Theory Comput. 2019 Oct 31. doi: 10.1021/acs.jctc.9b00987. PMID:31670957 doi:https://dx.doi.org/10.1021/acs.jctc.9b00987

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='6rt6' size='340' side='right'caption='[[6rt6]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rt6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RT6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RT6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rt6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RT6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RT6 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YTHDC1, KIAA1966, YT521 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6rt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rt6 OCA], [http://pdbe.org/6rt6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rt6 RCSB], [http://www.ebi.ac.uk/pdbsum/6rt6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rt6 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Bedi, R]]

6rt6: Difference between revisions

Revision as of 13:07, 18 December 2019

The YTH domain of YTHDC1 protein in complex with GGm6AC oligonucleotide

Structural highlights

Function

Publication Abstract from PubMed

References

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