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Structural basis for dimerization quality control.

ABSTRACT: Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration¹. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition², but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF-FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCF-FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF-FBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules.

SUBMITTER: Mena EL

PROVIDER: S-EPMC8024055 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Structural basis for dimerization quality control.

Mena Elijah L EL Jevtić Predrag P Greber Basil J BJ Gee Christine L CL Lew Brandon G BG Akopian David D Nogales Eva E Kuriyan John J Rape Michael M

Nature 20200819 7829

Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration<sup>1</sup>. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition<sup>2</sup>, but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing ...[more]

PMID: 32814905

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