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PDBsum entry 4f52
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Cell cycle/ligase/signaling protein
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PDB id
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4f52
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Contents |
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258 a.a.
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84 a.a.
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85 a.a.
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523 a.a.
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PDB id:
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| Name: |
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Cell cycle/ligase/signaling protein
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Title:
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Structure of a glomulin-rbx1-cul1 complex
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Structure:
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Cullin-1. Chain: a, c. Fragment: c-terminal domain, delta whb domain, unp residues 411-690. Synonym: cul-1. Engineered: yes. Mutation: yes. E3 ubiquitin-protein ligase rbx1. Chain: b, d. Fragment: unp residues 5-108.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: cul1. Expressed in: escherichia coli. Expression_system_taxid: 511693. Gene: rbx1, rnf75, roc1. Expression_system_taxid: 562. Gene: glmn, fap48, fap68, vmglom.
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Resolution:
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3.00Å
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R-factor:
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0.222
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R-free:
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0.289
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Authors:
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D.M.Duda,J.L.Olszewski,B.A.Schulman
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Key ref:
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D.M.Duda
et al.
(2012).
Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface.
Mol Cell,
47,
371-382.
PubMed id:
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Date:
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11-May-12
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Release date:
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19-Sep-12
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PROCHECK
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Headers
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References
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Q13616
(CUL1_HUMAN) -
Cullin-1 from Homo sapiens
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Seq:
Struc:
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776 a.a.
258 a.a.*
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P62877
(RBX1_HUMAN) -
E3 ubiquitin-protein ligase RBX1 from Homo sapiens
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Seq:
Struc:
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108 a.a.
84 a.a.
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Enzyme class 2:
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Chains A, C, E, F:
E.C.?
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Enzyme class 3:
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Chains B, D:
E.C.2.3.2.27
- RING-type E3 ubiquitin transferase.
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Reaction:
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6- ubiquitinyl-[acceptor protein]-L-lysine
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Enzyme class 4:
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Chains B, D:
E.C.2.3.2.32
- cullin-RING-type E3 NEDD8 transferase.
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Reaction:
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S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]- L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + N6-[NEDD8- protein]-yl-[cullin]-L-lysine
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Mol Cell
47:371-382
(2012)
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PubMed id:
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Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface.
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D.M.Duda,
J.L.Olszewski,
A.E.Tron,
M.Hammel,
L.J.Lambert,
M.B.Waddell,
T.Mittag,
J.A.DeCaprio,
B.A.Schulman.
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ABSTRACT
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The approximately 300 human cullin-RING ligases (CRLs) are multisubunit E3s in
which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze
ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds
RBX1's RING domain, regulates the RBX1-CUL1-containing SCF(FBW7) complex, and is
disrupted in the disease Glomuvenous Malformation. Here we report the crystal
structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural
and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that
tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain
formation by the E2 CDC34. The structure explains the basis for GLMN's
selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt
GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase
regulation, whereby an inhibitor blocks E2 access, and raises the possibility
that other E3s are likewise controlled by cellular proteins that mask E2-binding
surfaces to mediate inhibition.
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