4F52: Structure Of A Glomulin-Rbx1-Cul1 Complex

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.
PDB ID: 4F52Download
MMDB ID: 103054
PDB Deposition Date: 2012/5/11
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 4F52: trimeric; determined by author and by software (PISA)
Molecular Components in 4F52
Label Count Molecule
Proteins (3 molecules)
Cullin-1(Gene symbol: CUL1)
Molecule annotation
E3 Ubiquitin-protein Ligase Rbx1(Gene symbol: RBX1)
Molecule annotation
Glomulin(Gene symbol: GLMN)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB