3HQH: Structures Of Spop-substrate Complexes: Insights Into Molecular Architectures Of Btb-cul3 Ubiquitin Ligases: Spopmathx- Macroh2asbcpep1

In the largest E3 ligase subfamily, Cul3 binds a BTB domain, and an associated protein-interaction domain such as MATH recruits substrates for ubiquitination. Here, we present biochemical and structural analyses of the MATH-BTB protein, SPOP. We define a SPOP-binding consensus (SBC) and determine structures revealing recognition of SBCs from the phosphatase Puc, the transcriptional regulator Ci, and the chromatin component MacroH2A. We identify a dimeric SPOP-Cul3 assembly involving a conserved helical structure C-terminal of BTB domains, which we call "3-box" due to its facilitating Cul3 binding and its resemblance to F-/SOCS-boxes in other cullin-based E3s. Structural flexibility between the substrate-binding MATH and Cul3-binding BTB/3-box domains potentially allows a SPOP dimer to engage multiple SBCs found within a single substrate, such as Puc. These studies provide a molecular understanding of how MATH-BTB proteins recruit substrates to Cul3 and how their dimerization and conformational variability may facilitate avid interactions with diverse substrates.
PDB ID: 3HQHDownload
MMDB ID: 77512
PDB Deposition Date: 2009/6/6
Updated in MMDB: 2009/10
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3HQH: dimeric; determined by author and by software (PISA)
Molecular Components in 3HQH
Label Count Molecule
Proteins (2 molecules)
Speckle-type POZ Protein(Gene symbol: SPOP)
Molecule annotation
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB