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- EMDB-33608: The cryo-EM structure of human ERAD retro-translocation complex -
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Open data
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Basic information
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Title | The cryo-EM structure of human ERAD retro-translocation complex | |||||||||
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![]() | ERAD / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() Derlin-1-VIMP complex / Hrd1p ubiquitin ligase ERAD-L complex / endoplasmic reticulum quality control compartment / signal recognition particle binding / misfolded protein binding / positive regulation of Lys63-specific deubiquitinase activity / flavin adenine dinucleotide catabolic process / positive regulation of oxidative phosphorylation / VCP-NSFL1C complex / protein-DNA covalent cross-linking repair ...Derlin-1-VIMP complex / Hrd1p ubiquitin ligase ERAD-L complex / endoplasmic reticulum quality control compartment / signal recognition particle binding / misfolded protein binding / positive regulation of Lys63-specific deubiquitinase activity / flavin adenine dinucleotide catabolic process / positive regulation of oxidative phosphorylation / VCP-NSFL1C complex / protein-DNA covalent cross-linking repair / endoplasmic reticulum stress-induced pre-emptive quality control / endosome to lysosome transport via multivesicular body sorting pathway / cellular response to arsenite ion / Derlin-1 retrotranslocation complex / BAT3 complex binding / positive regulation of protein K63-linked deubiquitination / deubiquitinase activator activity / aggresome assembly / regulation of protein localization to chromatin / vesicle-fusing ATPase / mitotic spindle disassembly / VCP-NPL4-UFD1 AAA ATPase complex / NADH metabolic process / cellular response to misfolded protein / stress granule disassembly / K48-linked polyubiquitin modification-dependent protein binding / positive regulation of mitochondrial membrane potential / negative regulation of protein localization to chromatin / ubiquitin-modified protein reader activity / retrograde protein transport, ER to cytosol / regulation of aerobic respiration / positive regulation of ATP biosynthetic process / regulation of synapse organization / ATPase complex / ubiquitin-specific protease binding / ubiquitin-like protein ligase binding / MHC class I protein binding / RHOH GTPase cycle / autophagosome maturation / response to unfolded protein / HSF1 activation / polyubiquitin modification-dependent protein binding / proteasomal protein catabolic process / Protein methylation / endoplasmic reticulum to Golgi vesicle-mediated transport / translesion synthesis / interstrand cross-link repair / negative regulation of smoothened signaling pathway / ERAD pathway / ATP metabolic process / endoplasmic reticulum unfolded protein response / Attachment and Entry / viral genome replication / proteasome complex / lipid droplet / Josephin domain DUBs / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / positive regulation of protein ubiquitination / Hh mutants are degraded by ERAD / macroautophagy / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / Translesion Synthesis by POLH / protein destabilization / positive regulation of protein-containing complex assembly / establishment of protein localization / ABC-family proteins mediated transport / ADP binding / autophagy / Aggrephagy / cytoplasmic stress granule / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of protein catabolic process / activation of cysteine-type endopeptidase activity involved in apoptotic process / KEAP1-NFE2L2 pathway / azurophil granule lumen / double-strand break repair / Ovarian tumor domain proteases / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of canonical Wnt signaling pathway / late endosome / E3 ubiquitin ligases ubiquitinate target proteins / Neddylation / signaling receptor activity / site of double-strand break / cellular response to heat / ATPase binding / ubiquitin-dependent protein catabolic process / regulation of apoptotic process / protein phosphatase binding / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / protease binding / ficolin-1-rich granule lumen / Attachment and Entry / early endosome / protein ubiquitination / protein domain specific binding / intracellular membrane-bounded organelle / DNA repair Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.67 Å | |||||||||
![]() | Cao Y / Rao B / Wang Q / Yao D / Xia Y / Li W / Li S / Shen Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The cryo-EM structure of the human ERAD retrotranslocation complex. Authors: Bing Rao / Qian Wang / Deqiang Yao / Ying Xia / Wenguo Li / Yuming Xie / Shaobai Li / Mi Cao / Yafeng Shen / An Qin / Jie Zhao / Yu Cao / ![]() Abstract: Endoplasmic reticulum-associated degradation (ERAD) maintains protein homeostasis by retrieving misfolded proteins from the endoplasmic reticulum (ER) lumen into the cytosol for degradation. The ...Endoplasmic reticulum-associated degradation (ERAD) maintains protein homeostasis by retrieving misfolded proteins from the endoplasmic reticulum (ER) lumen into the cytosol for degradation. The retrotranslocation of misfolded proteins across the ER membrane is an energy-consuming process, with the detailed transportation mechanism still needing clarification. We determined the cryo-EM structures of the hetero-decameric complex formed by the Derlin-1 tetramer and the p97 hexamer. It showed an intriguing asymmetric complex and a putative coordinated squeezing movement in Derlin-1 and p97 parts. With the conformational changes of p97 induced by its ATP hydrolysis activities, the Derlin-1 channel could be torn into a "U" shape with a large opening to the lipidic environment, thereby forming an entry for the substrates in the ER membrane. The EM analysis showed that p97 formed a functional protein complex with Derlin-1, revealing the coupling mechanism between the ERAD retrotranslocation and the ATP hydrolysis activities. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 118.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.7 KB 17.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.9 KB | Display | ![]() |
Images | ![]() | 153 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
Others | ![]() ![]() | 116 MB 116 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 19.2 KB | Display | |
Data in CIF | ![]() | 24.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7y4wMC ![]() 7y53C ![]() 7y59C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33608_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33608_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : The cryo-EM structure of human ERAD retro-translocation complex
Entire | Name: The cryo-EM structure of human ERAD retro-translocation complex |
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Components |
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-Supramolecule #1: The cryo-EM structure of human ERAD retro-translocation complex
Supramolecule | Name: The cryo-EM structure of human ERAD retro-translocation complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 650 KDa |
-Macromolecule #1: Derlin-1
Macromolecule | Name: Derlin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.4781 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSDIGDWFRS IPAITRYWFA ATVAVPLVGK LGLISPAYLF LWPEAFLYRF QIWRPITATF YFPVGPGTGF LYLVNLYFLY QYSTRLETG AFDGRPADYL FMLLFNWICI VITGLAMDMQ LLMIPLIMSV LYVWAQLNRD MIVSFWFGTR FKACYLPWVI L GFNYIIGG ...String: MSDIGDWFRS IPAITRYWFA ATVAVPLVGK LGLISPAYLF LWPEAFLYRF QIWRPITATF YFPVGPGTGF LYLVNLYFLY QYSTRLETG AFDGRPADYL FMLLFNWICI VITGLAMDMQ LLMIPLIMSV LYVWAQLNRD MIVSFWFGTR FKACYLPWVI L GFNYIIGG SVINELIGNL VGHLYFFLMF RYPMDLGGRN FLSTPQFLYR WLPSRRHNWG QGFRLGDQ UniProtKB: Derlin-1 |
-Macromolecule #2: Transitional endoplasmic reticulum ATPase
Macromolecule | Name: Transitional endoplasmic reticulum ATPase / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO / EC number: vesicle-fusing ATPase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 87.546711 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MNRPNRLIVD EAINEDNSVV SLSQPKMDEL QLFRGDTVLL KGKKRREAVC IVLSDDTCSD EKIRMNRVVR NNLRVRLGDV ISIQPCPDV KYGKRIHVLP IDDTVEGITG NLFEVYLKPY FLEAYRPIRK GDIFLVRGGM RAVEFKVVET DPSPYCIVAP D TVIHCEGE ...String: MNRPNRLIVD EAINEDNSVV SLSQPKMDEL QLFRGDTVLL KGKKRREAVC IVLSDDTCSD EKIRMNRVVR NNLRVRLGDV ISIQPCPDV KYGKRIHVLP IDDTVEGITG NLFEVYLKPY FLEAYRPIRK GDIFLVRGGM RAVEFKVVET DPSPYCIVAP D TVIHCEGE PIKREDEEES LNEVGYDDIG GCRKQLAQIK EMVELPLRHP ALFKAIGVKP PRGILLYGPP GTGKTLIARA VA NETGAFF FLINGPEIMS KLAGESESNL RKAFEEAEKN APAIIFIDEL DAIAPKREKT HGEVERRIVS QLLTLMDGLK QRA HVIVMA ATNRPNSIDP ALRRFGRFDR EVDIGIPDAT GRLEILQIHT KNMKLADDVD LEQVANETHG HVGADLAALC SEAA LQAIR KKMDLIDLED ETIDAEVMNS LAVTMDDFRW ALSQSNPSAL RETVVEVPQV TWEDIGGLED VKRELQELVQ YPVEH PDKF LKFGMTPSKG VLFYGPPGCG KTLLAKAIAN ECQANFISIK GPELLTMWFG ESEANVREIF DKARQAAPCV LFFDEL DSI AKARGGNIGD GGGAADRVIN QILTEMDGMS TKKNVFIIGA TNRPDIIDPA ILRPGRLDQL IYIPLPDEKS RVAILKA NL RKSPVAKDVD LEFLAKMTNG FSGADLTEIC QRACKLAIRE SIESEIRRER ERQTNPSAME VEEDDPVPEI RRDHFEEA M RFARRSVSDN DIRKYEMFAQ TLQQSRGFGS FRFPSGNQGG AGPSQGSGGG TGGSVYTEDN DDDLYG UniProtKB: Transitional endoplasmic reticulum ATPase |
-Macromolecule #3: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 4 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ![]() ChemComp-ADP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 15 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 90 sec. / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 15 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average exposure time: 2.9 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |