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-FBXL1

SUBMITTER: Mena EL 

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

REPOSITORIES: biostudies-literature