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Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.

Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA
Mol Cell 36 39-50 (2009)
Related entries: 3hqi, 3hql, 3hqm, 3hsv, 3htm, 3hu6, 3hve, 3ivq, 3ivv

Cited: 290 times
EuropePMC logo PMID: 19818708

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.

Articles - 3hqh mentioned but not cited (5)

  1. Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA. Mol Cell 36 39-50 (2009)
  2. Phosphorylation within Intrinsic Disordered Region Discriminates Histone Variant macroH2A1 Splicing Isoforms-macroH2A1.1 and macroH2A1.2. Giallongo S, Lo Re O, Lochmanová G, Parca L, Petrizzelli F, Zdráhal Z, Mazza T, Vinciguerra M. Biology (Basel) 10 659 (2021)
  3. research-article 3D structural human interactome reveals proteome-wide perturbations by disease mutations. Xiong D, Zhao J, Qiu Y, Zhou Y, Lee D, Gupta S, Lu W, Liang S, Kang JJ, Eng C, Loscalzo J, Cheng F, Yu H. bioRxiv 2023.04.24.538110 (2023)
  4. Addressing the Binding Mechanism of the Meprin and TRAF-C Homology Domain of the Speckle-Type POZ Protein Using Protein Engineering. Diop A, Pietrangeli P, Pennacchietti V, Pagano L, Toto A, Di Felice M, Di Matteo S, Marcocci L, Malagrinò F, Gianni S. Int J Mol Sci 24 17364 (2023)
  5. Biophysical Characterization of the Binding Mechanism between the MATH Domain of SPOP and Its Physiological Partners. Diop A, Pietrangeli P, Nardella C, Pennacchietti V, Pagano L, Toto A, Di Felice M, Di Matteo S, Marcocci L, Malagrinò F, Gianni S. Int J Mol Sci 24 10138 (2023)


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Articles citing this publication (216)

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