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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 | ![]() negative regulation of nodal signaling pathway / multi-pass transmembrane protein insertion into ER membrane / multi-pass translocon complex / endoplasmic reticulum Sec complex / pronephric nephron development / determination of left/right asymmetry in lateral mesoderm / protein localization to nuclear inner membrane / rough endoplasmic reticulum membrane / endoplasmic reticulum quality control compartment / cotranslational protein targeting to membrane ...negative regulation of nodal signaling pathway / multi-pass transmembrane protein insertion into ER membrane / multi-pass translocon complex / endoplasmic reticulum Sec complex / pronephric nephron development / determination of left/right asymmetry in lateral mesoderm / protein localization to nuclear inner membrane / rough endoplasmic reticulum membrane / endoplasmic reticulum quality control compartment / cotranslational protein targeting to membrane / Ssh1 translocon complex / Sec61 translocon complex / protein targeting to ER / protein insertion into ER membrane / post-translational protein targeting to endoplasmic reticulum membrane / regulation of protein complex stability / SRP-dependent cotranslational protein targeting to membrane, translocation / embryonic brain development / signal sequence binding / SRP-dependent cotranslational protein targeting to membrane / eukaryotic 80S initiation complex / negative regulation of protein neddylation / post-translational protein targeting to membrane, translocation / axial mesoderm development / negative regulation of formation of translation preinitiation complex / endoplasmic reticulum calcium ion homeostasis / endoplasmic reticulum organization / 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 / GAIT complex / A band / positive regulation of DNA damage response, signal transduction by p53 class mediator / protein folding chaperone complex / TORC2 complex binding / alpha-beta T cell differentiation / middle ear morphogenesis / exit from mitosis / translation at presynapse / epidermal growth factor binding / retrograde protein transport, ER to cytosol / optic nerve development / cytoplasmic side of rough endoplasmic reticulum membrane / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / retinal ganglion cell axon guidance / negative regulation of ubiquitin protein ligase activity / ER overload response / homeostatic process / response to aldosterone / macrophage chemotaxis / lung morphogenesis / Protein hydroxylation / 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 / Response of EIF2AK4 (GCN2) to amino acid deficiency / protein transmembrane transporter activity / SRP-dependent cotranslational protein targeting to membrane / blastocyst development / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / regulation of signal transduction / L13a-mediated translational silencing of Ceruloplasmin expression / regulation of protein-containing complex assembly / Major pathway of rRNA processing in the nucleolus and cytosol / protein targeting / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / maturation of LSU-rRNA / rough endoplasmic reticulum / translation regulator activity / ERAD pathway / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / MDM2/MDM4 family protein binding / cytosolic ribosome / embryo implantation / protein folding chaperone / cellular response to interleukin-4 / ossification / innate immune response in mucosa / DNA damage response, signal transduction by p53 class mediator / guanyl-nucleotide exchange factor activity / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / regulation of signal transduction by p53 class mediator / positive regulation of translation / post-embryonic development / mRNA 3'-UTR binding / skeletal system development / sensory perception of sound / mitochondrial membrane / cellular response to gamma radiation / bone development / calcium ion transmembrane transport 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
Movie |
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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
Arichive directory | ![]() ![]() | HTTPS FTP |
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-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 




#55: Chemical | ChemComp-MG / #56: Chemical | #57: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-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 | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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