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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 / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair ...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 / 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 respiratory burst involved in inflammatory response / positive regulation of gastrulation / positive regulation of ubiquitin-protein transferase activity / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of DNA-templated transcription initiation / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / TNFR1-mediated ceramide production / mRNA stabilization / negative regulation of RNA splicing / post-transcriptional regulation of gene expression / neural crest cell differentiation / supercoiled DNA binding / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / protein kinase A binding / laminin receptor activity / pigmentation / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization / Translation initiation complex formation / TORC1 signaling / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / Protein hydroxylation / positive regulation of macroautophagy / BH3 domain binding / monocyte chemotaxis / negative regulation of translational frameshifting / ribosomal small subunit binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of translational initiation / TOR signaling / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / positive regulation of GTPase activity / iron-sulfur cluster binding / regulation of cell division / cellular response to ethanol / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / negative regulation of protein binding / protein serine/threonine kinase inhibitor activity / Eukaryotic Translation Termination / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of respiratory burst involved in inflammatory response / ubiquitin ligase inhibitor activity / Viral mRNA Translation / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / negative regulation of ubiquitin-dependent protein catabolic process / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of signal transduction by p53 class mediator / GTP hydrolysis and joining of the 60S ribosomal subunit / positive regulation of viral genome replication / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / positive regulation of microtubule polymerization / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / spindle assembly / 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) / Nuclear events stimulated by ALK signaling in cancer / translation regulator activity / rough endoplasmic reticulum / positive regulation of cell cycle / laminin binding / ribosomal small subunit export from nucleus / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / translation initiation factor 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. | ||||||
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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
