- EMDB-71810: Human 19S proteasome bound to TXNL1 PITH domain and PSMD5 -
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Basic information
Entry
Database: EMDB / ID: EMD-71810
Title
Human 19S proteasome bound to TXNL1 PITH domain and PSMD5
Map data
Sample
Complex: Human proteasome from HCT116 cells
Protein or peptide: x 20 types
Ligand: x 4 types
Keywords
Proteasome / 19S / RP / TXNL1 / PSMD5 / HYDROLASE
Function / homology
Function and homology information
proteasome regulatory particle assembly / disulfide oxidoreductase activity / positive regulation of inclusion body assembly / thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / proteasome accessory complex / integrator complex ...proteasome regulatory particle assembly / disulfide oxidoreductase activity / positive regulation of inclusion body assembly / thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / proteasome accessory complex / integrator complex / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / transcription factor binding / proteasome-activating activity / RND1 GTPase cycle / RND2 GTPase cycle / RND3 GTPase cycle / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / negative regulation of programmed cell death / RHOBTB1 GTPase cycle / protein K63-linked deubiquitination / RHOV GTPase cycle / metal-dependent deubiquitinase activity / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / cellular response to type I interferon / Cross-presentation of soluble exogenous antigens (endosomes) / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / Somitogenesis / K63-linked deubiquitinase activity / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / proteasome binding / RHOU GTPase cycle / Impaired BRCA2 binding to RAD51 / protein-disulfide reductase activity / positive regulation of RNA polymerase II transcription preinitiation complex assembly / general transcription initiation factor binding / Presynaptic phase of homologous DNA pairing and strand exchange / proteasome storage granule / polyubiquitin modification-dependent protein binding / protein deubiquitination / RHOBTB2 GTPase cycle / endopeptidase activator activity / proteasome assembly / mRNA export from nucleus / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / stem cell differentiation / regulation of macroautophagy / proteasome complex / enzyme regulator activity / ERAD pathway / inclusion body / TBP-class protein binding / regulation of proteasomal protein catabolic process / Regulation of activated PAK-2p34 by proteasome mediated degradation / ubiquitin binding / Autodegradation of Cdh1 by Cdh1:APC/C / proteasomal protein catabolic process / APC/C:Cdc20 mediated degradation of Securin / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / P-body / Vpu mediated degradation of CD4 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of DVL / Degradation of AXIN / Degradation of CRY and PER proteins / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / G2/M Checkpoints / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / Autodegradation of the E3 ubiquitin ligase COP1 / Regulation of RUNX3 expression and activity / Defective CFTR causes cystic fibrosis / double-strand break repair via homologous recombination / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) / Hedgehog 'on' state / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Vif-mediated degradation of APOBEC3G / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / double-strand break repair via nonhomologous end joining Similarity search - Function
National Institutes of Health/National Cancer Institute (NIH/NCI)
1 ZIABC011490
United States
Citation
Journal: Mol Cell / Year: 2026 Title: Structures of dynamic interactors at native proteasomes by PhIX-MS and cryo-electron microscopy. Authors: Kitaik Lee / Hitendra Negi / Xiang Chen / Katerina Atallah-Yunes / Sophia Truslow / Rithik E Castelino / Mary R Guest / Anthony M Ciancone / Xiuxiu Lu / Sergey G Tarasov / Raj Chari / Kylie ...Authors: Kitaik Lee / Hitendra Negi / Xiang Chen / Katerina Atallah-Yunes / Sophia Truslow / Rithik E Castelino / Mary R Guest / Anthony M Ciancone / Xiuxiu Lu / Sergey G Tarasov / Raj Chari / Kylie J Walters / Francis J O'Reilly / Abstract: Molecular machines rely on dynamic, low-affinity interactions to perform their functional roles. We developed PhIX-MS (photo-induced in situ crosslinking-mass spectrometry), a structural proteomics ...Molecular machines rely on dynamic, low-affinity interactions to perform their functional roles. We developed PhIX-MS (photo-induced in situ crosslinking-mass spectrometry), a structural proteomics workflow to capture topological information for such transient interactions in cells by UV-activated crosslinking. Applying PhIX-MS with cryo-electron microscopy (cryo-EM) to proteasomes, we mapped the redox sensor TXNL1 at the proteasome regulatory particle (RP), including its dynamic thioredoxin-like domain near RPN2/PSMD1 and RPN13/ADRM1, where it is ideal for reducing substrates prior to proteolysis. RPs without the proteolytic core particle (CP) were structurally resolved while bound to TXNL1 and/or the chaperone PSMD5/S5b, which inserts its C terminus into the ATPase pore, causing extensive structural rearrangements. Additionally, PhIX-MS and AlphaFold identified the ubiquitin ligase UBE3C/Hul5 at RPN2, RPN3, and a dynamic RPN10 region, tethering UBE3C above the substrate entry channel. Our integrative approach enables the localization of native, low-affinity protein interactions and is broadly applicable to dynamic macromolecular assemblies.
Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 295.15 K / Instrument: LEICA EM GP
Details
Quantifoil copper R 1.2/1.3 holey carbon 300 mesh grids (#Q3100CR1.3; Electron Microscopy Sciences).
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Electron microscopy
Microscope
FEI TALOS ARCTICA
Specialist optics
Energy filter - Name: GIF Bioquantum
Image recording
Film or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number real images: 40 / Average exposure time: 2.5 sec. / Average electron dose: 55.6 e/Å2
Electron beam
Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
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