View source for 6swa


==Mus musculus brain neocortex ribosome 60S bound to Ebp1==
<StructureSection load='6swa' size='340' side='right'caption='[[6swa]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6swa]] is a 46 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SWA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6swa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6swa OCA], [https://pdbe.org/6swa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6swa RCSB], [https://www.ebi.ac.uk/pdbsum/6swa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6swa ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/RL36_MOUSE RL36_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:Q9Y3U8] [[https://www.uniprot.org/uniprot/RL35_MOUSE RL35_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P42766] [[https://www.uniprot.org/uniprot/RL29_MOUSE RL29_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P47914] [[https://www.uniprot.org/uniprot/RL3_MOUSE RL3_MOUSE]] The L3 protein is a component of the large subunit of cytoplasmic ribosomes.[UniProtKB:P39023] [[https://www.uniprot.org/uniprot/RL8_MOUSE RL8_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P62917] [[https://www.uniprot.org/uniprot/RL21_MOUSE RL21_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P46778] [[https://www.uniprot.org/uniprot/RL35A_MOUSE RL35A_MOUSE]] Required for the proliferation and viability of hematopoietic cells. Plays a role in 60S ribosomal subunit formation. The protein was found to bind to both initiator and elongator tRNAs and consequently was assigned to the P site or P and A site. [[https://www.uniprot.org/uniprot/RL18_MOUSE RL18_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:Q07020] [[https://www.uniprot.org/uniprot/RL13A_MOUSE RL13A_MOUSE]] Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the ribosome and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. In the GAIT complex interacts with m7G cap-bound eIF4G at or near the eIF3-binding site and blocks the recruitment of the 43S ribosomal complex.<ref>PMID:23071094</ref>  [[https://www.uniprot.org/uniprot/RL11_MOUSE RL11_MOUSE]] 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. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs. It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:21804542). Promotes nucleolar location of PML (PubMed:15195100).<ref>PMID:15195100</ref> <ref>PMID:21804542</ref>  [[https://www.uniprot.org/uniprot/RL34_MOUSE RL34_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P49207] [[https://www.uniprot.org/uniprot/RL28_MOUSE RL28_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P46779] [[https://www.uniprot.org/uniprot/RL23A_MOUSE RL23A_MOUSE]] Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Binds a specific region on the 26S rRNA (By similarity). May promote p53/TP53 degradation possibly through the stimulation of MDM2-mediated TP53 polyubiquitination (By similarity).[UniProtKB:P62750] [[https://www.uniprot.org/uniprot/PA2G4_MOUSE PA2G4_MOUSE]] May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly (By similarity). Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site). Together with PTBP1 is required for the translation initiation on the foot-and-mouth disease virus (FMDV) IRES.<ref>PMID:10950867</ref> <ref>PMID:17690690</ref>  [[https://www.uniprot.org/uniprot/RL7_MOUSE RL7_MOUSE]] Component of the large ribosomal subunit (By similarity). Binds to G-rich structures in 28S rRNA and in mRNAs. Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs (By similarity).[UniProtKB:P18124] [[https://www.uniprot.org/uniprot/RL10_MOUSE RL10_MOUSE]] Component of the large ribosomal subunit. Plays a role in the formation of actively translating ribosomes. May play a role in the embryonic brain development.[UniProtKB:P27635] [[https://www.uniprot.org/uniprot/RL14_MOUSE RL14_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P50914] [[https://www.uniprot.org/uniprot/RL17_MOUSE RL17_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:P18621] [[https://www.uniprot.org/uniprot/RL41_MOUSE RL41_MOUSE]] Interacts with the beta subunit of protein kinase CKII and stimulates phosphorylation of DNA topoisomerase II alpha by CKII. [[https://www.uniprot.org/uniprot/RL5_MOUSE RL5_MOUSE]] 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. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs. It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53. Interacts with RRP1B.[UniProtKB:P46777] [[https://www.uniprot.org/uniprot/RL37_MOUSE RL37_MOUSE]] Binds to the 23S rRNA. [[https://www.uniprot.org/uniprot/RL6_MOUSE RL6_MOUSE]] Component of the large ribosomal subunit.[UniProtKB:Q02878] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein synthesis must be finely tuned in the developing nervous system as the final essential step of gene expression. This study investigates the architecture of ribosomes from the neocortex during neurogenesis, revealing Ebp1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest during start codon initiation and N-terminal peptide elongation, regulating ribosome occupancy of these codons. Membrane-targeting domains emerging from the 60S tunnel, which recruit SRP/Sec61 to the shared binding site, displace Ebp1. Ebp1 is particularly abundant in the early-born neural stem cell (NSC) lineage and regulates neuronal morphology. Ebp1 especially impacts the synthesis of membrane-targeted cell adhesion molecules (CAMs), measured by pulsed stable isotope labeling by amino acids in cell culture (pSILAC)/bioorthogonal noncanonical amino acid tagging (BONCAT) mass spectrometry (MS). Therefore, Ebp1 is a central component of protein synthesis, and the ribosome TE is a focal point of gene expression control in the molecular specification of neuronal morphology during development.

Protein Synthesis in the Developing Neocortex at Near-Atomic Resolution Reveals Ebp1-Mediated Neuronal Proteostasis at the 60S Tunnel Exit.,Kraushar ML, Krupp F, Harnett D, Turko P, Ambrozkiewicz MC, Sprink T, Imami K, Gunnigmann M, Zinnall U, Vieira-Vieira CH, Schaub T, Munster-Wandowski A, Burger J, Borisova E, Yamamoto H, Rasin MR, Ohler U, Beule D, Mielke T, Tarabykin V, Landthaler M, Kramer G, Vida I, Selbach M, Spahn CMT Mol Cell. 2021 Jan 21;81(2):304-322.e16. doi: 10.1016/j.molcel.2020.11.037. Epub , 2020 Dec 22. PMID:33357414<ref>PMID:33357414</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6swa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Kraushar, M L]]
[[Category: Sprink, T]]
[[Category: Ebp1]]
[[Category: Neocortex]]
[[Category: Neurodevelopment]]
[[Category: Peptide tunnel exit]]
[[Category: Ribosome]]