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Open data
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Basic information
Entry | Database: PDB / ID: 6w6l | ||||||||||||||||||
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Title | Cryo-EM structure of the human ribosome-TMCO1 translocon | ||||||||||||||||||
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![]() | RIBOSOME/PROTEIN TRANSPORT / RIBOSOME-PROTEIN TRANSPORT complex | ||||||||||||||||||
Function / homology | ![]() : / endoplasmic reticulum Sec complex / pronephric nephron development / endoplasmic reticulum quality control compartment / : / rough endoplasmic reticulum membrane / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER ...: / endoplasmic reticulum Sec complex / pronephric nephron development / endoplasmic reticulum quality control compartment / : / rough endoplasmic reticulum membrane / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER / protein insertion into ER membrane / regulation of protein complex stability / embryonic brain development / eukaryotic 80S initiation complex / post-translational protein targeting to endoplasmic reticulum membrane / negative regulation of protein neddylation / translation at presynapse / axial mesoderm development / negative regulation of formation of translation preinitiation complex / SRP-dependent cotranslational protein targeting to membrane / 90S preribosome assembly / signal sequence binding / TORC2 complex binding / endoplasmic reticulum organization / endoplasmic reticulum calcium ion homeostasis / post-translational protein targeting to membrane, translocation / SRP-dependent cotranslational protein targeting to membrane, translocation / GAIT complex / middle ear morphogenesis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / alpha-beta T cell differentiation / exit from mitosis / 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 / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / epidermal growth factor binding / negative regulation of ubiquitin protein ligase activity / optic nerve development / retrograde protein transport, ER to cytosol / response to aldosterone / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / retinal ganglion cell axon guidance / homeostatic process / lung morphogenesis / ER overload response / Protein hydroxylation / macrophage chemotaxis / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / protein localization to nucleus / L13a-mediated translational silencing of Ceruloplasmin expression / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / GTP hydrolysis and joining of the 60S ribosomal subunit / protein transmembrane transporter activity / regulation of signal transduction / regulation of protein-containing complex assembly / protein-RNA complex assembly / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / protein targeting / cellular response to interleukin-4 / translation regulator activity / cytosolic ribosome / ERAD pathway / rough endoplasmic reticulum / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / embryo implantation / negative regulation of ubiquitin-dependent protein catabolic process / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ossification / post-embryonic development / maturation of LSU-rRNA / innate immune response in mucosa / ribosomal large subunit biogenesis / regulation of signal transduction by p53 class mediator / mRNA 3'-UTR binding / skeletal system development / positive regulation of translation / calcium ion transmembrane transport / sensory perception of sound / calcium channel activity / bone development / ribosomal large subunit assembly / cellular response to gamma radiation / mRNA 5'-UTR binding / Regulation of expression of SLITs and ROBOs / cytoplasmic ribonucleoprotein granule / cellular response to type II interferon / intracellular calcium ion homeostasis Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.84 Å | ||||||||||||||||||
![]() | Keenan, R.J. / McGilvray, P.T. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: An ER translocon for multi-pass membrane protein biogenesis. Authors: Philip T McGilvray / S Andrei Anghel / Arunkumar Sundaram / Frank Zhong / Michael J Trnka / James R Fuller / Hong Hu / Alma L Burlingame / Robert J Keenan / ![]() Abstract: Membrane proteins with multiple transmembrane domains play critical roles in cell physiology, but little is known about the machinery coordinating their biogenesis at the endoplasmic reticulum. Here ...Membrane proteins with multiple transmembrane domains play critical roles in cell physiology, but little is known about the machinery coordinating their biogenesis at the endoplasmic reticulum. Here we describe a ~ 360 kDa ribosome-associated complex comprising the core Sec61 channel and five accessory factors: TMCO1, CCDC47 and the Nicalin-TMEM147-NOMO complex. Cryo-electron microscopy reveals a large assembly at the ribosome exit tunnel organized around a central membrane cavity. Similar to protein-conducting channels that facilitate movement of transmembrane segments, cytosolic and luminal funnels in TMCO1 and TMEM147, respectively, suggest routes into the central membrane cavity. High-throughput mRNA sequencing shows selective translocon engagement with hundreds of different multi-pass membrane proteins. Consistent with a role in multi-pass membrane protein biogenesis, cells lacking different accessory components show reduced levels of one such client, the glutamate transporter EAAT1. These results identify a new human translocon and provide a molecular framework for understanding its role in multi-pass membrane protein biogenesis. | ||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 5.4 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 243.2 KB | Display | |
Data in CIF | ![]() | 430.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 21435MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
+60S ribosomal protein ... , 41 types, 41 molecules ABCFGHIJKLMNOPQRSTUVWXYZabcdef...
-RNA chain , 5 types, 5 molecules DEtuv
#4: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#5: RNA chain | Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#44: RNA chain | Mass: 1159525.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#45: RNA chain | Mass: 24414.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#46: RNA chain | Mass: 24436.508 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein/peptide , 1 types, 1 molecules y
#47: Protein/peptide | Mass: 2315.846 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-Protein transport protein Sec61 subunit ... , 3 types, 3 molecules 123
#48: Protein | Mass: 52295.379 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#49: Protein | Mass: 7752.325 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#50: Protein | Mass: 9987.456 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 4 types, 4 molecules 4576
#51: Protein | Mass: 25279.848 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#52: Protein | Mass: 63047.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#53: Protein | Mass: 55946.762 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#54: Protein | Mass: 21205.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 3 types, 32 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/HOH.gif)
#55: Chemical | ChemComp-MG / #56: Chemical | #57: Water | ChemComp-HOH / | |
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-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 |
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Sample preparation
Component | Name: human ribosome-TMCO1 translocon / Type: COMPLEX / Entity ID: #1-#54 / Source: NATURAL | |||||||||||||||||||||||||
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Molecular weight | Value: 4 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.4 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: The sample was well dispersed on a thin carbon film | |||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: C-flat-1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K Details: Two filter papers were added to each arm, 2.5 microliters of sample were added to the grids, and 0.5 seconds of drain time was allowed before vitrification. |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 3.8 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5562 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1049128 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.84 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 82684 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL Details: Starting models: 60S ribosomal subunit, tRNAs and nascent chain from 6om0. Sec61 heterotrimer from 6fti. Nicalin, TMEM147 are iTasser homology models based on 5a63. TMCO1 and CCDC47 are co- ...Details: Starting models: 60S ribosomal subunit, tRNAs and nascent chain from 6om0. Sec61 heterotrimer from 6fti. Nicalin, TMEM147 are iTasser homology models based on 5a63. TMCO1 and CCDC47 are co-evolution-based models from RaptorX-Contact. | ||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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