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Open data
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Basic information
| Entry | Database: PDB / ID: 8xp2 | ||||||
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| Title | Cryo-EM structure of the human 40S ribosome with LARP1 | ||||||
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Keywords | RIBOSOME / 40S ribosome / LARP1 / mTOR | ||||||
| Function / homology | Function and homology informationcellular response to rapamycin / translation activator activity / eukaryotic initiation factor 4E binding / RNA cap binding / response to amino acid starvation / RNA 7-methylguanosine cap binding / TORC1 signaling / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist ...cellular response to rapamycin / translation activator activity / eukaryotic initiation factor 4E binding / RNA cap binding / response to amino acid starvation / RNA 7-methylguanosine cap binding / TORC1 signaling / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / mRNA stabilization / TNFR1-mediated ceramide production / positive regulation of ubiquitin-protein transferase activity / nucleolus organization / positive regulation of DNA-templated transcription initiation / negative regulation of RNA splicing / negative regulation of DNA repair / post-transcriptional regulation of gene expression / erythrocyte homeostasis / supercoiled DNA binding / regulation of establishment of cell polarity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / NF-kappaB complex / cytoplasmic translational initiation / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of phagocytosis / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / cytoplasmic side of rough endoplasmic reticulum membrane / ribosomal small subunit binding / Formation of the ternary complex, and subsequently, the 43S complex / laminin receptor activity / negative regulation of myoblast fusion / ion channel inhibitor activity / positive regulation of mitochondrial depolarization / protein kinase A binding / Ribosomal scanning and start codon recognition / positive regulation of macroautophagy / Translation initiation complex formation / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / Protein hydroxylation / TOR signaling / negative regulation of translational frameshifting / BH3 domain binding / iron-sulfur cluster binding / monocyte chemotaxis / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / mTORC1-mediated signalling / gastrulation / SARS-CoV-1 modulates host translation machinery / regulation of cell division / positive regulation of GTPase activity / Peptide chain elongation / cellular response to ethanol / Selenocysteine synthesis / positive regulation of translational initiation / Formation of a pool of free 40S subunits / negative regulation of protein binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / protein serine/threonine kinase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / Eukaryotic Translation Termination / Dengue Virus Attachment and Entry / negative regulation of ubiquitin-dependent protein catabolic process / ubiquitin ligase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Viral mRNA Translation / positive regulation of signal transduction by p53 class mediator / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / positive regulation of viral genome replication / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / positive regulation of microtubule polymerization / spindle assembly / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / positive regulation of intrinsic apoptotic signaling pathway / Protein methylation / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / translation regulator activity / Nuclear events stimulated by ALK signaling in cancer / rough endoplasmic reticulum / ribosomal small subunit export from nucleus / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / laminin binding Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Huang, Z. / Ye, X. / Li, Y. / Cheng, J. | ||||||
| Funding support | 1items
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Citation | Journal: EMBO J / Year: 2024Title: LARP1 binds ribosomes and TOP mRNAs in repressed complexes. Authors: James A Saba / Zixuan Huang / Kate L Schole / Xianwen Ye / Shrey D Bhatt / Yi Li / Winston Timp / Jingdong Cheng / Rachel Green / ![]() Abstract: Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in ...Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in 40S- or 80S-ribosome complexes that are thought to repress and stabilize TOPs. However, a molecular understanding of how LARP1 and TOPs interact with these ribosome complexes is lacking. Here, we show that LARP1 directly binds non-translating ribosomal subunits. Cryo-EM structures reveal a previously uncharacterized domain of LARP1 bound to and occluding the mRNA channel of the 40S subunit. Increased availability of free ribosomal subunits downstream of various stresses promote 60S joining at the same interface to form LARP1-80S complexes. Simultaneously, LARP1 engages the TOP via its previously characterized La/PAM2 and DM15 domains. Contrary to expectations, ribosome binding within these complexes is not required for LARP1-mediated TOP repression or stabilization, two canonical LARP1 functions. Together, this work provides molecular insight into how LARP1 directly binds ribosomal subunits and challenges existing models describing the function of repressed LARP1-40S/80S-TOP complexes. | ||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8xp2.cif.gz | 1.7 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8xp2.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8xp2.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xp/8xp2 ftp://data.pdbj.org/pub/pdb/validation_reports/xp/8xp2 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 38548MC ![]() 8xp3C M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
+40S ribosomal protein ... , 31 types, 31 molecules SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-Protein , 3 types, 3 molecules SgSfJD
| #23: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
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| #35: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
| #36: Protein | Mass: 123705.344 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q6PKG0 |
-Protein/peptide / RNA chain / Non-polymers , 3 types, 6 molecules LnS2

| #1: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62945 |
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| #2: RNA chain | Mass: 602752.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 36162 |
| #37: Chemical | ChemComp-ZN / |
-Details
| Has ligand of interest | N |
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| Has protein modification | N |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: LARP1-40S ribosome / Type: RIBOSOME / Details: 40S ribosome with LARP1 / Entity ID: #1-#36 / Source: NATURAL |
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| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
| Vitrification | Cryogen name: ETHANE / Humidity: 100 % |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Specimen holder | Cryogen: NITROGEN |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
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| CTF correction | Details: Relion / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 1906164 | ||||||||||||||||||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 25959 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
| Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
| Atomic model building | PDB-ID: 6Z6M Accession code: 6Z6M / Source name: PDB / Type: experimental model |
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Homo sapiens (human)
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FIELD EMISSION GUN
