4F52

Structure of a Glomulin-RBX1-CUL1 complex

Summary for 4F52

• Entry DOI: 10.2210/pdb4f52/pdb
• Descriptor: Cullin-1, E3 ubiquitin-protein ligase RBX1, Glomulin, ... (4 entities in total)
• Functional Keywords: cullin-ring e3 ligase, inhibitor, cell cycle-ligase-signaling protein complex, cell cycle/ligase/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P62877
• Total number of polymer chains: 6
• Total formula weight: 226362.20

Authors

Duda, D.M.,Olszewski, J.L.,Schulman, B.A. (deposition date: 2012-05-11, release date: 2012-09-19, Last modification date: 2024-02-28)

Primary citation

Duda, D.M.,Olszewski, J.L.,Tron, A.E.,Hammel, M.,Lambert, L.J.,Waddell, M.B.,Mittag, T.,Decaprio, J.A.,Schulman, B.A.
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, 2012

PubMed Abstract: 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.

PubMed: 22748924
DOI: 10.1016/j.molcel.2012.05.044

Experimental method

X-RAY DIFFRACTION (3 Å)