› 7b5l

Electron Microscopy
3.8Å resolution

Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transition State 1

Released:
DOI: 10.2210/pdb7b5l/pdb
PDB entry 7b5l coloured by chain, front view.
PDB entry 7b5l coloured by chain, side view.
PDB entry 7b5l coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Ubiquitin ligation to F-box protein targets by SCF-RBR E3-E3 super-assembly.
Horn-Ghetko D, Krist DT, Prabu JR, Baek K, Mulder MPC, Klügel M, Scott DC, Ovaa H, Kleiger G, Schulman BA
Nature 590 671-676 (2021)
PMID: 33536622
Related structures: EMD-12037

Function and Biology Details

Reactions catalysed: 
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RBR-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine
S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + N(6)-[NEDD8-protein]-yl-[cullin]-L-lysine
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dodecamer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-143342 (preferred)
Entry contents:
12 distinct polypeptide molecules
Macromolecules (12 distinct):
Cullin-1 Chain: C
Molecule details ›
Chain: C
Length: 776 amino acids
Theoretical weight: 89.8 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: Q13616 (Residues: 1-776; Coverage: 100%)
Gene name: CUL1
Sequence domains:
E3 ubiquitin-protein ligase ARIH1 Chain: H
Molecule details ›
Chain: H
Length: 557 amino acids
Theoretical weight: 64.2 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y4X5 (Residues: 1-557; Coverage: 100%)
Gene names: ARI, ARIH1, HUSSY-27, MOP6, UBCH7BP
Sequence domains:
S-phase kinase-associated protein 2 Chain: T
Molecule details ›
Chain: T
Length: 424 amino acids
Theoretical weight: 47.82 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q13309 (Residues: 1-424; Coverage: 100%)
Gene names: FBXL1, SKP2
Sequence domains: F-box-like
Cyclin-dependent kinases regulatory subunit 1 Chain: K
Molecule details ›
Chain: K
Length: 73 amino acids
Theoretical weight: 8.97 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P61024 (Residues: 1-73; Coverage: 92%)
Gene names: CKS1, CKS1B, PNAS-143, PNAS-16
Sequence domains: Cyclin-dependent kinase regulatory subunit
S-phase kinase-associated protein 1 Chain: S
Molecule details ›
Chain: S
Length: 163 amino acids
Theoretical weight: 18.68 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P63208 (Residues: 1-163; Coverage: 100%)
Gene names: EMC19, OCP2, SKP1, SKP1A, TCEB1L
Sequence domains:
Ubiquitin Chain: U
Molecule details ›
Chain: U
Length: 75 amino acids
Theoretical weight: 8.52 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P0CG48 (Residues: 609-683; Coverage: 11%)
Gene name: UBC
Sequence domains: Ubiquitin family
NEDD8 Chain: N
Molecule details ›
Chain: N
Length: 76 amino acids
Theoretical weight: 8.57 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q15843 (Residues: 1-76; Coverage: 94%)
Gene name: NEDD8
Sequence domains: Ubiquitin family
E3 ubiquitin-protein ligase RBX1 Chain: R
Molecule details ›
Chain: R
Length: 108 amino acids
Theoretical weight: 12.29 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P62877 (Residues: 1-108; Coverage: 100%)
Gene names: RBX1, RNF75, ROC1
Sequence domains: RING-H2 zinc finger domain
Ubiquitin-conjugating enzyme E2 L3 Chain: D
Molecule details ›
Chain: D
Length: 154 amino acids
Theoretical weight: 17.83 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P68036 (Residues: 1-154; Coverage: 100%)
Gene names: UBCE7, UBCH7, UBE2L3
Sequence domains: Ubiquitin-conjugating enzyme
Cyclin-dependent kinase 2 Chain: L
Molecule details ›
Chain: L
Length: 298 amino acids
Theoretical weight: 34.06 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P24941 (Residues: 1-298; Coverage: 100%)
Gene names: CDK2, CDKN2
Sequence domains: Protein kinase domain
Cyclin-A2 Chain: Y
Molecule details ›
Chain: Y
Length: 432 amino acids
Theoretical weight: 48.61 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P20248 (Residues: 1-432; Coverage: 100%)
Gene names: CCN1, CCNA, CCNA2
Sequence domains:
Cyclin-dependent kinase inhibitor 1B Chain: P
Molecule details ›
Chain: P
Length: 198 amino acids
Theoretical weight: 22.19 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P46527 (Residues: 1-198; Coverage: 100%)
Gene names: CDKN1B, KIP1, p27
Sequence domains: Cyclin-dependent kinase inhibitor

Ligands and Environments

2 bound ligands:
Ligand ZN 9 x ZN
Ligand SY8 1 x SY8
1 modified residue:
Ligand TPO 2 x TPO

Experiments and Validation Details

Entry percentile scores
Resolution: 3.8Å
Relevant EMDB volumes: EMD-12037
Expression systems:
  • Trichoplusia ni
  • Escherichia coli

Quick links

Citations

17 review citations

PROTAC targeted protein degraders: the past is prologue.
Békés et al. (2022)
16 more

8 mentions without citation

Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain.
Reiter et al. (2022)
7 more