6zot: Difference between revisions
m Protected "6zot" [edit=sysop:move=sysop] |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of YTHDF3 YTH domain in complex with m6A RNA== | |||
<StructureSection load='6zot' size='340' side='right'caption='[[6zot]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6zot]] is a 3 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=6ZOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZOT 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]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</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=6zot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zot OCA], [https://pdbe.org/6zot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zot RCSB], [https://www.ebi.ac.uk/pdbsum/6zot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zot ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/YTHD3_HUMAN YTHD3_HUMAN] Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28106072, PubMed:28106076, PubMed:28281539, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:28106072, PubMed:28281539, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3 (PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:28106076, PubMed:32492408). Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs (By similarity). Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification (By similarity). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (PubMed:28106072). Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (PubMed:28281539). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31388144, PubMed:31292544, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation (PubMed:32194978).[UniProtKB:Q8BYK6]<ref>PMID:22575960</ref> <ref>PMID:24284625</ref> <ref>PMID:28106072</ref> <ref>PMID:28106076</ref> <ref>PMID:28281539</ref> <ref>PMID:31292544</ref> <ref>PMID:31388144</ref> <ref>PMID:32194978</ref> <ref>PMID:32451507</ref> <ref>PMID:32492408</ref> Has some antiviral activity against HIV-1 virus: incorporated into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity in the next cycle of infection (PubMed:32053707). May interfere with this early step of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome (PubMed:32053707).<ref>PMID:32053707</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Three YTH-domain family proteins (YTHDF1, YTHDF2, and YTHDF3) recognize the N(6)-methyladenosine (m(6)A) modification of mRNA in cells. However, the redundancy of their cellular functions has been disputed. We investigate their interactions with m(6)A-containing RNA using X-ray crystallography and molecular dynamics (MD). The new X-ray structures and MD simulations show that the three proteins share identical interactions with the m(6)A-containing RNA and have similar intrinsic plasticity, thus evidencing the redundant roles of the three proteins in cellular functions. | |||
Structural and Dynamic Insights into Redundant Function of YTHDF Proteins.,Li Y, Bedi RK, Moroz-Omori EV, Caflisch A J Chem Inf Model. 2020 Dec 28;60(12):5932-5935. doi: 10.1021/acs.jcim.0c01029. , Epub 2020 Oct 19. PMID:33073985<ref>PMID:33073985</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6zot" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bedi RK]] | |||
[[Category: Caflisch A]] | |||