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| | <StructureSection load='6yam' size='340' side='right'caption='[[6yam]], [[Resolution|resolution]] 3.60Å' scene=''> | | <StructureSection load='6yam' size='340' side='right'caption='[[6yam]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6yam]] is a 50 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YAM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YAM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yam]] 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=6YAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YAM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=C4J:'>C4J</scene>, <scene name='pdbligand=T6A:N-[N-(9-B-D-RIBOFURANOSYLPURIN-6-YL)CARBAMOYL]THREONINE-5-MONOPHOSPHATE'>T6A</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C4J:(2~{S})-2-azanyl-4-[5-[(2~{S},3~{R},4~{S},5~{S})-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]-3-methyl-2,6-bis(oxidanylidene)pyrimidin-1-yl]butanoic+acid'>C4J</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T6A:N-[N-(9-B-D-RIBOFURANOSYLPURIN-6-YL)CARBAMOYL]THREONINE-5-MONOPHOSPHATE'>T6A</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6yal|6yal]], [[6yan|6yan]]</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=6yam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yam OCA], [https://pdbe.org/6yam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yam RCSB], [https://www.ebi.ac.uk/pdbsum/6yam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yam ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yam OCA], [http://pdbe.org/6yam PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yam RCSB], [http://www.ebi.ac.uk/pdbsum/6yam PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yam ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Function == | + | <div style="background-color:#fffaf0;"> |
| - | [[http://www.uniprot.org/uniprot/G1U971_RABIT G1U971_RABIT]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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 preinitiation 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.[HAMAP-Rule:MF_03002] [[http://www.uniprot.org/uniprot/G1T3L2_RABIT G1T3L2_RABIT]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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 preinitiation 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.[HAMAP-Rule:MF_03010] [[http://www.uniprot.org/uniprot/G1SLC2_RABIT G1SLC2_RABIT]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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. 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.[HAMAP-Rule:MF_03005] [[http://www.uniprot.org/uniprot/G1SLW8_RABIT G1SLW8_RABIT]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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 preinitiation 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.[HAMAP-Rule:MF_03012] [[http://www.uniprot.org/uniprot/G1TLT8_RABIT G1TLT8_RABIT]] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria. Acts as a PPP1R16B-dependent substrate of PPP1CA.[HAMAP-Rule:MF_03016] [[http://www.uniprot.org/uniprot/G1TN72_RABIT G1TN72_RABIT]] May play a role during erythropoiesis through regulation of transcription factor DDIT3 (By similarity).[HAMAP-Rule:MF_03122] [[http://www.uniprot.org/uniprot/G1SUC8_RABIT G1SUC8_RABIT]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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 preinitiation 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. Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway. May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins.[HAMAP-Rule:MF_03004] [[http://www.uniprot.org/uniprot/A0A5F9C991_RABIT A0A5F9C991_RABIT]] RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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. 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.[HAMAP-Rule:MF_03000]
| + | == Publication Abstract from PubMed == |
| | + | In higher eukaryotes, the mRNA sequence in the direct vicinity of the start codon, called the Kozak sequence (CRCCaugG, where R is a purine), is known to influence the rate of the initiation process. However, the molecular basis underlying its role remains poorly understood. Here, we present the cryoelectron microscopy (cryo-EM) structures of mammalian late-stage 48S initiation complexes (LS48S ICs) in the presence of two different native mRNA sequences, beta-globin and histone 4, at overall resolution of 3 and 3.5 A, respectively. Our high-resolution structures unravel key interactions from the mRNA to eukaryotic initiation factors (eIFs): 1A, 2, 3, 18S rRNA, and several 40S ribosomal proteins. In addition, we are able to study the structural role of ABCE1 in the formation of native 48S ICs. Our results reveal a comprehensive map of ribosome/eIF-mRNA and ribosome/eIF-tRNA interactions and suggest the impact of mRNA sequence on the structure of the LS48S IC. |
| | + | |
| | + | Structural Insights into the Mammalian Late-Stage Initiation Complexes.,Simonetti A, Guca E, Bochler A, Kuhn L, Hashem Y Cell Rep. 2020 Apr 7;31(1):107497. doi: 10.1016/j.celrep.2020.03.061. PMID:32268096<ref>PMID:32268096</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6yam" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Bochler, A]] | + | [[Category: Bochler A]] |
| - | [[Category: Guca, E]] | + | [[Category: Guca E]] |
| - | [[Category: Hashem, Y]] | + | [[Category: Hashem Y]] |
| - | [[Category: Simonetti, A]] | + | [[Category: Simonetti A]] |
| - | [[Category: Eukaryotic initiation factor 1]]
| + | |
| - | [[Category: Eukaryotic initiation factor 1a]]
| + | |
| - | [[Category: Eukaryotic initiation factor 3]]
| + | |
| - | [[Category: Late-stage initiation complex]]
| + | |
| - | [[Category: Rabbit]]
| + | |
| - | [[Category: Translation]]
| + | |
| - | [[Category: Translation initiation]]
| + | |
