View source for 6ybs


==Structure of a human 48S translational initiation complex - head==
<StructureSection load='6ybs' size='340' side='right'caption='[[6ybs]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ybs]] is a 10 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=6YBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YBS 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=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=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=JMH:[(2~{R},3~{S},4~{R},5~{R})-5-(4-azanylidene-3-methyl-2-oxidanylidene-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>JMH</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</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=6ybs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ybs OCA], [https://pdbe.org/6ybs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ybs RCSB], [https://www.ebi.ac.uk/pdbsum/6ybs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ybs ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/EIF3D_HUMAN EIF3D_HUMAN] Defects in EIF3D are associated with some cancers, such as prostate, breast and colon cancers. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Down-regulation inhibits proliferation of cancers (PubMed:25322666, PubMed:25370813, PubMed:25682860, PubMed:26008152, PubMed:26036682, PubMed:26617750, PubMed:27035563).<ref>PMID:25322666</ref> <ref>PMID:25370813</ref> <ref>PMID:25682860</ref> <ref>PMID:26008152</ref> <ref>PMID:26036682</ref> <ref>PMID:26617750</ref> <ref>PMID:27035563</ref> 
== Function ==
[https://www.uniprot.org/uniprot/EIF3D_HUMAN EIF3D_HUMAN] mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815).<ref>PMID:18599441</ref> <ref>PMID:25849773</ref> <ref>PMID:27462815</ref>   (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426).<ref>PMID:18056426</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A key step in translational initiation is the recruitment of the 43S preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5' end of messenger RNA (mRNA) to form the 48S initiation complex (i.e., the 48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo-electron microscopy to determine the structure of a reconstituted human 48S The structure reveals insights into early events of translation initiation complex assembly, as well as how eIF4F interacts with subunits of eIF3 near the mRNA exit channel in the 43S The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests that downstream mRNA is unwound at least in part by being "pulled" through the 40S subunit during scanning.

Structure of a human 48S translational initiation complex.,Brito Querido J, Sokabe M, Kraatz S, Gordiyenko Y, Skehel JM, Fraser CS, Ramakrishnan V Science. 2020 Sep 4;369(6508):1220-1227. doi: 10.1126/science.aba4904. PMID:32883864<ref>PMID:32883864</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ybs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
*[[Ribosome 3D structures|Ribosome 3D structures]]
*[[3D sructureseceptor for activated protein kinase C 1|3D sructureseceptor for activated protein kinase C 1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brito Querido J]]
[[Category: Fraser C]]
[[Category: Gordiyenko Y]]
[[Category: Kraatz S]]
[[Category: Ramakrishnan V]]
[[Category: Skehel M]]
[[Category: Sokabe M]]