View source for 6qtz


==Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles==
<SX load='6qtz' size='340' side='right' viewer='molstar' caption='[[6qtz]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qtz]] is a 48 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_ Saccharomyces cerevisiae ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QTZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qtz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtz OCA], [http://pdbe.org/6qtz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qtz RCSB], [http://www.ebi.ac.uk/pdbsum/6qtz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtz ProSAT]</span></td></tr>
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== Function ==
[[http://www.uniprot.org/uniprot/REH1_YEAST REH1_YEAST]] Pre-60S-associated cytoplasmic factor involved in the cytoplasmic maturation of the 60S subunit. May act redundantly with REI1 to directly promote a stabilizing structural rearrangement in cytoplasmic 60S subunit maturation independent on the REI1-specific ARX1 recycling.<ref>PMID:19433447</ref>  [[http://www.uniprot.org/uniprot/RL25_YEAST RL25_YEAST]] This protein binds to a specific region on the 26S rRNA. [[http://www.uniprot.org/uniprot/RL40A_YEAST RL40A_YEAST]] 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).  60S ribosomal protein L40-A: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:22096102). eL40 is essential for translation of a subset of cellular transcripts, including stress response transcripts, such as DDR2 (PubMed:23169626).<ref>PMID:23169626</ref> <ref>PMID:22096102</ref>  [[http://www.uniprot.org/uniprot/IF6_YEAST IF6_YEAST]] Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by the GTPase RIA1/EFL1 and by SDO1. Also required for pre-rRNA processing.<ref>PMID:10085284</ref> <ref>PMID:11779510</ref> <ref>PMID:11238882</ref> <ref>PMID:17353896</ref> <ref>PMID:18256024</ref> <ref>PMID:11101899</ref>  [[http://www.uniprot.org/uniprot/RL16B_YEAST RL16B_YEAST]] Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel.<ref>PMID:22096102</ref>  [[http://www.uniprot.org/uniprot/NMD3_YEAST NMD3_YEAST]] Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit. Unlikely to play a significant role in nonsense-mediated mRNA decay (NMD).<ref>PMID:11086007</ref>  [[http://www.uniprot.org/uniprot/RL5_YEAST RL5_YEAST]] Binds 5S RNA and is required for 60S subunit assembly. [[http://www.uniprot.org/uniprot/RL4A_YEAST RL4A_YEAST]] Participates in the regulation of the accumulation of its own mRNA.<ref>PMID:2065661</ref>  [[http://www.uniprot.org/uniprot/RL37A_YEAST RL37A_YEAST]] Binds to the 23S rRNA (By similarity). [[http://www.uniprot.org/uniprot/LSG1_YEAST LSG1_YEAST]] GTPase required for the nuclear export of the 60S ribosomal subunit. Acts by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm.<ref>PMID:15660131</ref> <ref>PMID:15831484</ref> <ref>PMID:17015443</ref> <ref>PMID:17761675</ref>  [[http://www.uniprot.org/uniprot/RL11A_YEAST RL11A_YEAST]] Binds to 5S ribosomal RNA. 
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== Publication Abstract from PubMed ==
During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large ribosomal subunits. Here, we present the mechanism of peptidyltransferase centre (PTC) completion that explains how integration of the last ribosomal proteins is coupled to release of the nuclear export adaptor Nmd3. Single-particle cryo-EM reveals that eL40 recruitment stabilises helix 89 to form the uL16 binding site. The loading of uL16 unhooks helix 38 from Nmd3 to adopt its mature conformation. In turn, partial retraction of the L1 stalk is coupled to a conformational switch in Nmd3 that allows the uL16 P-site loop to fully accommodate into the PTC where it competes with Nmd3 for an overlapping binding site (base A2971). Our data reveal how the central functional site of the ribosome is sculpted and suggest how the formation of translation-competent 60S subunits is disrupted in leukaemia-associated ribosomopathies.

Mechanism of completion of peptidyltransferase centre assembly in eukaryotes.,Kargas V, Castro-Hartmann P, Escudero-Urquijo N, Dent K, Hilcenko C, Sailer C, Zisser G, Marques-Carvalho MJ, Pellegrino S, Wawiorka L, Freund SM, Wagstaff JL, Andreeva A, Faille A, Chen E, Stengel F, Bergler H, Warren AJ Elife. 2019 May 22;8. pii: 44904. doi: 10.7554/eLife.44904. PMID:31115337<ref>PMID:31115337</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Kargas, V]]
[[Category: Warren, A J]]
[[Category: 60s subunit]]
[[Category: Eif6]]
[[Category: Lsg1]]
[[Category: Nmd3]]
[[Category: Ribosome]]