View source for 7ucj


==Mammalian 80S translation initiation complex with mRNA and Harringtonine==
<StructureSection load='7ucj' size='340' side='right'caption='[[7ucj]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ucj]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UCJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MA:6-HYDRO-1-METHYLADENOSINE-5-MONOPHOSPHATE'>1MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=4AC:N(4)-ACETYLCYTIDINE-5-MONOPHOSPHATE'>4AC</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=B8H:[(2~{R},3~{S},4~{R},5~{S})-5-[1-methyl-2,4-bis(oxidanylidene)pyrimidin-5-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B8H</scene>, <scene name='pdbligand=B8K:[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-7-ethanoyl-6-oxidanylidene-1,8-dihydropurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B8K</scene>, <scene name='pdbligand=B8N:(2~{R})-2-azanyl-4-[5-[(2~{S},3~{R},4~{S},5~{R})-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]-3-methyl-2,6-bis(oxidanylidene)pyrimidin-1-yl]butanoic+acid'>B8N</scene>, <scene name='pdbligand=B8Q:[(2~{R},3~{S},4~{R},5~{R})-5-(4-azanyl-3-methyl-2-oxidanylidene-4~{H}-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B8Q</scene>, <scene name='pdbligand=B8T:[(2~{R},3~{S},4~{R},5~{R})-5-[4-(methylamino)-2-oxidanylidene-pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B8T</scene>, <scene name='pdbligand=B8W:[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-methoxy-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B8W</scene>, <scene name='pdbligand=B9B:[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-propoxy-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B9B</scene>, <scene name='pdbligand=B9H:[(2~{R},3~{R},4~{R},5~{R})-5-(4-azanyl-2-oxidanylidene-3-propyl-4~{H}-pyrimidin-1-yl)-4-methoxy-3-oxidanyl-oxolan-2-yl]methyl+dihydrogen+phosphate'>B9H</scene>, <scene name='pdbligand=BGH:[(2~{R},3~{R},4~{R},5~{R})-5-(2-azanyl-7-ethanoyl-6-oxidanylidene-1,8-dihydropurin-9-yl)-4-methoxy-3-oxidanyl-oxolan-2-yl]methyl+dihydrogen+phosphate'>BGH</scene>, <scene name='pdbligand=E6G:[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-ethoxy-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>E6G</scene>, <scene name='pdbligand=E7G:[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-7-ethyl-6-oxidanylidene-1,8-dihydropurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>E7G</scene>, <scene name='pdbligand=I4U:[(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-(2-oxidanylidene-4-propan-2-yloxy-pyrimidin-1-yl)oxolan-2-yl]methyl+dihydrogen+phosphate'>I4U</scene>, <scene name='pdbligand=M7A:[(2~{R},3~{S},4~{R},5~{R})-5-(6-azanyl-7-methyl-8~{H}-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>M7A</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MHG:[(2~{R},3~{S},4~{R},5~{R})-5-[2-(methylamino)-7-[(3~{S})-3-methylpentyl]-6-oxidanylidene-1,8-dihydropurin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>MHG</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=MMX:[(2~{R},3~{S},4~{R},5~{R})-5-[(4~{S})-4-azanyl-3-ethyl-2-oxidanylidene-1,3-diazinan-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>MMX</scene>, <scene name='pdbligand=MQ6:(9R)-O~3~-[(2S)-2,5-dihydroxy-2-(2-methoxy-2-oxoethyl)-5-methylhexanoyl]cephalotaxine'>MQ6</scene>, <scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=P4U:[(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-(2-oxidanylidene-4-propoxy-pyrimidin-1-yl)oxolan-2-yl]methyl+dihydrogen+phosphate'>P4U</scene>, <scene name='pdbligand=P7G:[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-oxidanylidene-7-propyl-3,8-dihydropurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>P7G</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=T6A:N-[N-(9-B-D-RIBOFURANOSYLPURIN-6-YL)CARBAMOYL]THREONINE-5-MONOPHOSPHATE'>T6A</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7ucj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ucj OCA], [https://pdbe.org/7ucj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ucj RCSB], [https://www.ebi.ac.uk/pdbsum/7ucj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ucj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL21_RABIT RL21_RABIT] Component of the large ribosomal subunit (PubMed:26245381, PubMed:27863242, PubMed:30517857). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:26245381, PubMed:27863242, PubMed:30517857).<ref>PMID:26245381</ref> <ref>PMID:27863242</ref> <ref>PMID:30517857</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent manner. Although cytidine acetylation (ac4C) within protein-coding sequences stimulates translation, ac4C within 5' UTRs impacts protein synthesis at the level of initiation. 5' UTR acetylation promotes initiation at upstream sequences, competitively inhibiting annotated start codons. Acetylation further directly impedes initiation at optimal AUG contexts: ac4C within AUG-flanking Kozak sequences reduced initiation in base-resolved transcriptome-wide HeLa results and in vitro utilizing substrates with site-specific ac4C incorporation. Cryo-EM of mammalian 80S initiation complexes revealed that ac4C in the -1 position adjacent to an AUG start codon disrupts an interaction between C and hypermodified t6A at nucleotide 37 of the initiator tRNA. These findings demonstrate the impact of RNA modifications on nucleobase function at a molecular level and introduce mRNA acetylation as a factor regulating translation in a location-specific manner.

Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine.,Arango D, Sturgill D, Yang R, Kanai T, Bauer P, Roy J, Wang Z, Hosogane M, Schiffers S, Oberdoerffer S Mol Cell. 2022 Aug 4;82(15):2797-2814.e11. doi: 10.1016/j.molcel.2022.05.016. , Epub 2022 Jun 8. PMID:35679869<ref>PMID:35679869</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ucj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Arango D]]
[[Category: Oberdoerffer S]]
[[Category: Sturgill D]]
[[Category: Yang R]]