Adaptor Protein Self-Assembly Drives the Control of a Cullin-RING Ubiquitin Ligase

• DOI: 10.1016/j.str.2012.04.009
• Publication Date: 2012-06-27T21:36:00Z
• Authors: Wesley J. Errington; M. Qasim Khan; Stephanie A. Bueler; John L. Rubinstein; Avijit Chakrabartty; Gilbert G. Privé
• Keywords: Cullin; Ubiquitin-Protein Ligases; DDB1

The E3 ligases recruit substrate proteins for targeted ubiquitylation. Recent insights into the mechanisms of ubiquitylation demonstrate that E3 ligases can possess active regulatory properties beyond those of a simple assembly scaffold. Here, we describe the dimeric structure of the E3 ligase adaptor protein SPOP (speckle-type POZ protein) in complex with the N-terminal domain of Cul3 at 2.4 Å resolution. We find that SPOP forms large oligomers that can form heteromeric species with the closely related paralog SPOPL. In combination, SPOP and SPOPL (SPOP-like) form a molecular rheostat that can fine-tune E3 ubiquitin ligase activity by affecting the oligomeric state of the E3 complex. We propose that adaptor protein self-assembly provides a graded level of regulation of the SPOP/Cul3 E3 ligase toward its multiple protein substrates.