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| <SX load='6gsn' size='340' side='right' viewer='molstar' caption='[[6gsn]], [[Resolution|resolution]] 5.75Å' scene=''> | | <SX load='6gsn' size='340' side='right' viewer='molstar' caption='[[6gsn]], [[Resolution|resolution]] 5.75Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6gsn]] is a 47 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Kluyveromyces_lactis_(strain_atcc_8585_/_cbs_2359_/_dsm_70799_/_nbrc_1267_/_nrrl_y-1140_/_wm37) Kluyveromyces lactis (strain atcc 8585 / cbs 2359 / dsm 70799 / nbrc 1267 / nrrl y-1140 / wm37)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GSN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6GSN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gsn]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Kluyveromyces_lactis_NRRL_Y-1140 Kluyveromyces lactis NRRL Y-1140]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GSN FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GCP:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>GCP</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 5.75Å</td></tr> |
- | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GCP:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>GCP</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jap|3jap]], [[3jaq|3jaq]]</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=6gsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gsn OCA], [https://pdbe.org/6gsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gsn RCSB], [https://www.ebi.ac.uk/pdbsum/6gsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gsn 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=6gsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gsn OCA], [http://pdbe.org/6gsn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gsn RCSB], [http://www.ebi.ac.uk/pdbsum/6gsn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gsn ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/IF1A_YEAST IF1A_YEAST]] Seems to be required for maximal rate of protein biosynthesis. Enhances ribosome dissociation into subunits and stabilizes the binding of the initiator Met-tRNA(I) to 40 S ribosomal subunits. [[http://www.uniprot.org/uniprot/IF2B_YEAST IF2B_YEAST]] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [[http://www.uniprot.org/uniprot/IF2A_YEAST IF2A_YEAST]] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [[http://www.uniprot.org/uniprot/IF2G_YEAST IF2G_YEAST]] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [[http://www.uniprot.org/uniprot/EIF3C_YEAST EIF3C_YEAST]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome.<ref>PMID:12651896</ref> [[http://www.uniprot.org/uniprot/SUI1_YEAST SUI1_YEAST]] Additional factor that functions in concert with eIF-2 and the initiator tRNA in directing the ribosome to the proper start site of translation. [[http://www.uniprot.org/uniprot/EIF3I_YEAS7 EIF3I_YEAS7]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome (By similarity). [[http://www.uniprot.org/uniprot/EIF3A_YEAST EIF3A_YEAST]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome.<ref>PMID:9694884</ref> <ref>PMID:11387228</ref> <ref>PMID:12651896</ref> <ref>PMID:18765792</ref> [[http://www.uniprot.org/uniprot/RSSA_KLULA RSSA_KLULA]] 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. [[http://www.uniprot.org/uniprot/RS21_KLULA RS21_KLULA]] Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Has a physiological role leading to 18S rRNA stability (By similarity). [[http://www.uniprot.org/uniprot/EIF3G_YEAS7 EIF3G_YEAS7]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. This subunit can bind 18S rRNA.[HAMAP-Rule:MF_03006] [[http://www.uniprot.org/uniprot/RS27A_KLULA RS27A_KLULA]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome. [[http://www.uniprot.org/uniprot/EIF3B_YEAST EIF3B_YEAST]] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome.<ref>PMID:11387228</ref> | + | [https://www.uniprot.org/uniprot/Q6CKL3_KLULA Q6CKL3_KLULA] |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
- | Translation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation, attaches to the 5' end of the mRNA and scans to locate the start codon, whereupon it closes to arrest scanning. We present single particle cryo-electron microscopy (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states, at 6.0 A and 4.9 A, respectively. These reconstructions show eIF2beta as well as a configuration of eIF3 that appears to encircle the 40S, occupying part of the subunit interface. Comparison of the complexes reveals a large conformational change in the 40S head from an open mRNA latch conformation to a closed one that constricts the mRNA entry channel and narrows the P site to enclose tRNAi, thus elucidating key events in start codon recognition.
| + | The eukaryotic initiation factor 3 (eIF3) complex is involved in every step of translation initiation, but there is limited understanding of its molecular functions. Here, we present a single particle electron cryomicroscopy (cryo-EM) reconstruction of yeast 48S ribosomal preinitiation complex (PIC) in an open conformation conducive to scanning, with core subunit eIF3b bound on the 40S interface near the decoding center in contact with the ternary complex eIF2.GTP.initiator tRNA. eIF3b is relocated together with eIF3i from their solvent interface locations observed in other PIC structures, with eIF3i lacking 40S contacts. Re-processing of micrographs of our previous 48S PIC in a closed state also suggests relocation of the entire eIF3b-3i-3g-3a-Cter module during the course of initiation. Genetic analysis indicates that high fidelity initiation depends on eIF3b interactions at the 40S subunit interface that promote the closed PIC conformation, or facilitate the relocation of eIF3b/eIF3i to the solvent interface, on start codon selection. |
| | | |
- | Conformational Differences between Open and Closed States of the Eukaryotic Translation Initiation Complex.,Llacer JL, Hussain T, Marler L, Aitken CE, Thakur A, Lorsch JR, Hinnebusch AG, Ramakrishnan V Mol Cell. 2015 Aug 6;59(3):399-412. doi: 10.1016/j.molcel.2015.06.033. Epub 2015 , Jul 23. PMID:26212456<ref>PMID:26212456</ref>
| + | Large-scale movement of eIF3 domains during translation initiation modulate start codon selection.,Llacer JL, Hussain T, Dong J, Villamayor L, Gordiyenko Y, Hinnebusch AG Nucleic Acids Res. 2021 Oct 14. pii: 6396891. doi: 10.1093/nar/gkab908. PMID:34648019<ref>PMID:34648019</ref> |
| | | |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
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| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
| + | [[Category: Kluyveromyces lactis NRRL Y-1140]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Hussain, T]] | + | [[Category: Hussain T]] |
- | [[Category: Llacer, J L]] | + | [[Category: Llacer JL]] |
- | [[Category: Ramakrishnan, V]] | + | [[Category: Ramakrishnan V]] |
- | [[Category: 48s pic]]
| + | |
- | [[Category: Eif1a]]
| + | |
- | [[Category: Eif2]]
| + | |
- | [[Category: Eif3]]
| + | |
- | [[Category: Initiation factor]]
| + | |
- | [[Category: Ribosome]]
| + | |
- | [[Category: Small ribosome subunit]]
| + | |
- | [[Category: Translation]]
| + | |
- | [[Category: Trnai]]
| + | |