Abstract
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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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Cullin Proteins / chemistry*
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Cullin Proteins / genetics
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Cullin Proteins / metabolism
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Escherichia coli
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Humans
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Models, Molecular
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Molecular Sequence Data
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Plasmids
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Protein Binding
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Multimerization
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins / chemistry*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sequence Alignment
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Structural Homology, Protein
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Ubiquitin / chemistry*
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Ubiquitin / genetics
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Ubiquitin / metabolism
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Ubiquitination
Substances
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CUL3 protein, human
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Cullin Proteins
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Nuclear Proteins
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Protein Isoforms
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Recombinant Proteins
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Repressor Proteins
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SPOP protein, human
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Ubiquitin