3HVE

Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases: GigaxoninBTB/3-box

Summary for 3HVE

• Entry DOI: 10.2210/pdb3hve/pdb
• Related: 3HQI 3HQL 3HQM 3HSV 3HTM 3HU6
• Descriptor: Gigaxonin (2 entities in total)
• Functional Keywords: ubiquitin, gigaxonin, cytoplasm, cytoskeleton, disease mutation, kelch repeat, neurodegeneration, phosphoprotein, polymorphism, ubl conjugation, ubl conjugation pathway, protein binding, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 57346.96

Authors

Zhuang, M.,Schulman, B.A. (deposition date: 2009-06-16, release date: 2009-10-27, Last modification date: 2024-10-30)

Primary citation

Zhuang, M.,Calabrese, M.F.,Liu, J.,Waddell, M.B.,Nourse, A.,Hammel, M.,Miller, D.J.,Walden, H.,Duda, D.M.,Seyedin, S.N.,Hoggard, T.,Harper, J.W.,White, K.P.,Schulman, B.A.
Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.
Mol.Cell, 36:39-50, 2009

PubMed Abstract: 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.

PubMed: 19818708
DOI: 10.1016/j.molcel.2009.09.022

Experimental method

X-RAY DIFFRACTION (2.8 Å)