Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases

摘要: 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 structural analyses of MATH-BTB protein, SPOP. We define SPOP-binding consensus (SBC) determine structures revealing recognition SBCs from phosphatase Puc, transcriptional regulator Ci, chromatin component MacroH2A. identify dimeric SPOP-Cul3 assembly involving conserved helical structure C-terminal domains, which call "3-box" due to its facilitating binding resemblance F-/SOCS-boxes in other cullin-based E3s. Structural flexibility between substrate-binding Cul3-binding BTB/3-box domains potentially allows SPOP dimer engage multiple found within single substrate, Puc. These studies provide molecular understanding how proteins recruit their dimerization conformational variability may facilitate avid interactions with diverse substrates.