+Open data
-Basic information
Entry | Database: PDB / ID: 8ony | ||||||
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Title | Human Methionine Aminopeptidase 2 at the 80S ribosome | ||||||
Components |
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Keywords | METAL BINDING PROTEIN / Ribosome Associated Factor / Protease / Tunnel exit / Protein Maturation / Proteostasis / NME / p67 / MAP / MetAP / MAP2 / MetAP2 / ES27L / PTE | ||||||
Function / homology | Function and homology information N-terminal protein amino acid modification / peptidyl-methionine modification / initiator methionyl aminopeptidase activity / eukaryotic 80S initiation complex / methionyl aminopeptidase / axial mesoderm development / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator ...N-terminal protein amino acid modification / peptidyl-methionine modification / initiator methionyl aminopeptidase activity / eukaryotic 80S initiation complex / methionyl aminopeptidase / axial mesoderm development / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / metalloexopeptidase activity / TORC2 complex binding / middle ear morphogenesis / Peptide chain elongation / Selenocysteine synthesis / metalloaminopeptidase activity / protein-RNA complex assembly / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / 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 / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / aminopeptidase activity / ribosomal large subunit biogenesis / ossification / cytosolic ribosome / positive regulation of translation / skeletal system development / sensory perception of sound / cellular response to gamma radiation / mRNA 5'-UTR binding / protein processing / rRNA processing / Regulation of expression of SLITs and ROBOs / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to UV / regulation of translation / cytoplasmic translation / cytosolic large ribosomal subunit / postsynaptic density / rRNA binding / structural constituent of ribosome / cadherin binding / ribonucleoprotein complex / translation / focal adhesion / mRNA binding / synapse / nucleolus / RNA binding / extracellular exosome / nucleoplasm / membrane / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.92 Å | ||||||
Authors | Klein, M.A. / Wild, K. / Kisonaite, M. / Sinning, I. | ||||||
Funding support | Germany, 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Methionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome. Authors: Marius A Klein / Klemens Wild / Miglė Kišonaitė / Irmgard Sinning / Abstract: Excision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine ...Excision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine aminopeptidases in eukaryotes (MAP1 and MAP2), additional roles in disease and translational regulation have drawn more attention to MAP2. Here, we report several cryo-EM structures of human and fungal MAP2 at the 80S ribosome. Irrespective of nascent chains, MAP2 can occupy the tunnel exit. On nascent chain displaying ribosomes, the MAP2-80S interaction is highly dynamic and the MAP2-specific N-terminal extension engages in stabilizing interactions with the long rRNA expansion segment ES27L. Loss of this extension by autoproteolytic cleavage impedes interactions at the tunnel, while promoting MAP2 to enter the ribosomal A-site, where it engages with crucial functional centers of translation. These findings reveal that proteolytic remodeling of MAP2 severely affects ribosome binding, and set the stage for targeted functional studies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ony.cif.gz | 381.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ony.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8ony.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/on/8ony ftp://data.pdbj.org/pub/pdb/validation_reports/on/8ony | HTTPS FTP |
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-Related structure data
Related structure data | 17002MC 8onxC 8onzC 8oo0C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 2 types, 2 molecules 58
#1: RNA chain | Mass: 1640222.125 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Production host: Thermochaetoides thermophila DSM 1495 (fungus) References: GenBank: NR_003287 |
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#7: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 555853 |
-60S ribosomal protein ... , 5 types, 5 molecules LkLYLhLXLR
#2: Protein | Mass: 8238.948 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63173 |
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#3: Protein | Mass: 17303.363 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61254 |
#4: Protein | Mass: 14593.624 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P42766 |
#5: Protein | Mass: 17740.193 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62750 |
#6: Protein | Mass: 23535.281 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P84098 |
-Protein / Non-polymers , 2 types, 3 molecules A
#8: Protein | Mass: 52971.523 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: METAP2, MNPEP, P67EIF2 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P50579, methionyl aminopeptidase |
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#9: Chemical |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: MAP2-80S ribosome complex / Type: RIBOSOME / Entity ID: #1-#8 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 FIELDBright-field microscopy / Nominal defocus max: 2100 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
EM software | Name: PHENIX / Version: 1.19_4092: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.92 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 215768 / Symmetry type: POINT | ||||||||||||||||||||||||
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