- EMDB-17822: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase... -
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Entry
Database: EMDB / ID: EMD-17822
Title
K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and Cdc34: NEDD8-CUL2-RBX1-ELOB/C-FEM1C with trapped UBE2R2-donor UB-acceptor UB-SIL1 peptide
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Sample
Complex: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and CDC34:NEDD8-CUL2-RBX1-ELOB/C-FEM1C with trapped UBE2R2-donor UB-acceptor UB-SIL1 peptide
Complex: RING E3 ligase (RBX1) and Cullin-2 (CUL2)
Protein or peptide: E3 ubiquitin-protein ligase RBX1
Protein or peptide: Cullin-2
Complex: CDC34, NEDD8, ELOB, ELOC, FEM1C with UBE2R2-donor UB-acceptor UB-SIL1 peptide and K48-linked ubiquitin chain
Protein or peptide: Ubiquitin-conjugating enzyme E2 R2
Protein or peptide: Polyubiquitin-C,Nucleotide exchange factor SIL1
adenyl-nucleotide exchange factor activity / cotranslational protein targeting to membrane / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / target-directed miRNA degradation ...adenyl-nucleotide exchange factor activity / cotranslational protein targeting to membrane / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / E2 ubiquitin-conjugating enzyme / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / ubiquitin conjugating enzyme activity / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / protein K48-linked ubiquitination / Formation of HIV elongation complex in the absence of HIV Tat / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / RNA Polymerase II Pre-transcription Events / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / positive regulation of TORC1 signaling / T cell activation / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / Regulation of PTEN localization / NRIF signals cell death from the nucleus / Regulation of BACH1 activity / Activated NOTCH1 Transmits Signal to the Nucleus / intrinsic apoptotic signaling pathway / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / TICAM1, RIP1-mediated IKK complex recruitment / cellular response to amino acid stimulus / Downregulation of TGF-beta receptor signaling / EGFR downregulation Similarity search - Function
Journal: Nat Struct Mol Biol / Year: 2024 Title: Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases. Authors: Joanna Liwocha / Jerry Li / Nicholas Purser / Chutima Rattanasopa / Samuel Maiwald / David T Krist / Daniel C Scott / Barbara Steigenberger / J Rajan Prabu / Brenda A Schulman / Gary Kleiger / Abstract: E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked ...E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked poly-ubiquitin chains to control an enormous swath of eukaryotic biology. Yet the molecular mechanisms underlying this exceptional linkage specificity and millisecond kinetics of poly-ubiquitylation remain unclear. Here we obtain cryogenic-electron microscopy (cryo-EM) structures that provide pertinent insight into how such poly-ubiquitin chains are forged. The CRL RING domain not only activates the E2-bound ubiquitin but also shapes the conformation of a distinctive UBE2R2 loop, positioning both the ubiquitin to be transferred and the substrate-linked acceptor ubiquitin within the active site. The structures also reveal how the ubiquitin-like protein NEDD8 uniquely activates CRLs during chain formation. NEDD8 releases the RING domain from the CRL, but unlike previous CRL-E2 structures, does not contact UBE2R2. These findings suggest how poly-ubiquitylation may be accomplished by many E2s and E3s.
Entire : K48-linked ubiquitin chain formation with a cullin-RING E3 ligase...
Entire
Name: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and CDC34:NEDD8-CUL2-RBX1-ELOB/C-FEM1C with trapped UBE2R2-donor UB-acceptor UB-SIL1 peptide
Components
Complex: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and CDC34:NEDD8-CUL2-RBX1-ELOB/C-FEM1C with trapped UBE2R2-donor UB-acceptor UB-SIL1 peptide
Complex: RING E3 ligase (RBX1) and Cullin-2 (CUL2)
Protein or peptide: E3 ubiquitin-protein ligase RBX1
Protein or peptide: Cullin-2
Complex: CDC34, NEDD8, ELOB, ELOC, FEM1C with UBE2R2-donor UB-acceptor UB-SIL1 peptide and K48-linked ubiquitin chain
Protein or peptide: Ubiquitin-conjugating enzyme E2 R2
Protein or peptide: Polyubiquitin-C,Nucleotide exchange factor SIL1
Protein or peptide: Protein fem-1 homolog C
Protein or peptide: Ubiquitin
Protein or peptide: Elongin-C
Protein or peptide: Elongin-B
Ligand: 5-azanylpentan-2-one
Ligand: ZINC ION
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Supramolecule #1: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase...
Supramolecule
Name: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and CDC34:NEDD8-CUL2-RBX1-ELOB/C-FEM1C with trapped UBE2R2-donor UB-acceptor UB-SIL1 peptide type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#8
Molecular weight
Theoretical: 190 KDa
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Supramolecule #2: RING E3 ligase (RBX1) and Cullin-2 (CUL2)
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