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

Zhuang, M. et al. (2009) Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Molecular Cell, 36(1), pp. 39-50. (doi: 10.1016/j.molcel.2009.09.022) (PMID:19818708) (PMCID:PMC2847577)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walden, Professor Helen
Authors: 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., and Schulman, B. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Molecular Cell
Publisher:Elsevier
ISSN:1097-2765
ISSN (Online):1097-4164
Published Online:08 October 2009

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