- EMDB-3313: Cryo-EM structure of CSN-N8-CRL4A at 6.7 A resolution -
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Basic information
Entry
Database: EMDB / ID: EMD-3313
Title
Cryo-EM structure of CSN-N8-CRL4A at 6.7 A resolution
Map data
Cryo-EM structure of CSN-N8-CRL4 at 6.7 A resolution
Sample
Sample: Recombinant human CSN-N8-CRL4A complex
Protein or peptide: x 12 types
Keywords
COP9 Signalosome / Cullin-RING ligases / Cryo-EM
Function / homology
Function and homology information
Prolactin receptor signaling / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / Regulation of BACH1 activity / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / Formation of TC-NER Pre-Incision Complex / trophectodermal cell proliferation / Dual Incision in GG-NER / Dual incision in TC-NER ...Prolactin receptor signaling / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / Regulation of BACH1 activity / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / Formation of TC-NER Pre-Incision Complex / trophectodermal cell proliferation / Dual Incision in GG-NER / Dual incision in TC-NER / Formation of Incision Complex in GG-NER / macrophage migration inhibitory factor binding / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / Regulation of RUNX2 expression and activity / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of DVL / Orc1 removal from chromatin / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / regulation of IRE1-mediated unfolded protein response / Hedgehog 'on' state / negative regulation of granulocyte differentiation / Degradation of beta-catenin by the destruction complex / exosomal secretion / eukaryotic initiation factor 4E binding / deNEDDylase activity / GTPase inhibitor activity / Interleukin-1 signaling / regulation of protein neddylation / eukaryotic translation initiation factor 3 complex / KEAP1-NFE2L2 pathway / anaphase-promoting complex / protein deneddylation / GLI3 is processed to GLI3R by the proteasome / cullin-RING-type E3 NEDD8 transferase / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / cullin-RING ubiquitin ligase complex / positive regulation by virus of viral protein levels in host cell / regulation of DNA damage checkpoint / COP9 signalosome / regulation of nucleotide-excision repair / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / activation of NF-kappaB-inducing kinase activity / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / regulation of proteolysis / VCB complex / Cul4-RING E3 ubiquitin ligase complex / positive regulation of protein autoubiquitination / UV-damage excision repair / protein neddylation / metal-dependent deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases) / NEDD8 ligase activity / biological process involved in interaction with symbiont / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / inner cell mass cell proliferation / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / protein deubiquitination / negative regulation of reproductive process / negative regulation of developmental process / skeletal muscle cell differentiation / TGF-beta receptor signaling activates SMADs / protein monoubiquitination / somatic stem cell population maintenance / cullin family protein binding / regulation of JNK cascade / hemopoiesis / viral release from host cell / response to light stimulus / ectopic germ cell programmed cell death / proteasomal protein catabolic process / positive regulation of viral genome replication / positive regulation of G1/S transition of mitotic cell cycle / anatomical structure morphogenesis / protein K48-linked ubiquitination / ubiquitin ligase complex / JNK cascade / positive regulation of gluconeogenesis / positive regulation of TORC1 signaling / T cell activation / translation initiation factor activity / intrinsic apoptotic signaling pathway / post-translational protein modification Similarity search - Function
Journal: Nature / Year: 2016 Title: Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. Authors: Simone Cavadini / Eric S Fischer / Richard D Bunker / Alessandro Potenza / Gondichatnahalli M Lingaraju / Kenneth N Goldie / Weaam I Mohamed / Mahamadou Faty / Georg Petzold / Rohan E J ...Authors: Simone Cavadini / Eric S Fischer / Richard D Bunker / Alessandro Potenza / Gondichatnahalli M Lingaraju / Kenneth N Goldie / Weaam I Mohamed / Mahamadou Faty / Georg Petzold / Rohan E J Beckwith / Ritesh B Tichkule / Ulrich Hassiepen / Wassim Abdulrahman / Radosav S Pantelic / Syota Matsumoto / Kaoru Sugasawa / Henning Stahlberg / Nicolas H Thomä / Abstract: The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A- ...The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 Å resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.
History
Deposition
Jan 30, 2016
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Header (metadata) release
Feb 24, 2016
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Map release
Apr 6, 2016
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Update
Apr 13, 2016
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Current status
Apr 13, 2016
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Details: Quantifoil holey carbon grids (R1.2/1.3, Cu 400 mesh) and Lacey carbons films
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 93 K / Instrument: LEICA EM GP / Method: Blot for 2 seconds before plunging
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Electron microscopy
Microscope
FEI TITAN KRIOS
Specialist optics
Energy filter - Name: Gatan Image Filter Quantum LS / Energy filter - Lower energy threshold: 0.0 eV / Energy filter - Upper energy threshold: 20.0 eV
Date
Jun 1, 2015
Image recording
Category: CCD / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number real images: 2626 Details: Every image is the average of 38 frames recorded by the direct electron detector
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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