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TitleStructural basis for dimerization quality control.
Journal, issue, pagesNature, Vol. 586, Issue 7829, Page 452-456, Year 2020
Publish dateAug 19, 2020
AuthorsElijah L Mena / Predrag Jevtić / Basil J Greber / Christine L Gee / Brandon G Lew / David Akopian / Eva Nogales / John Kuriyan / Michael Rape /
PubMed AbstractMost quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of ...Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition, 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.
External linksNature / PubMed:32814905 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.2 - 8.5 Å
Structure data

21617

6wcq

EMDB-21617, PDB-6wcq:
Structure of a substrate-bound DQC ubiquitin ligase
Method: EM (single particle) / Resolution: 8.5 Å

PDB-6w66:
The structure of the F64A, S172A mutant Keap1-BTB domain in complex with SKP1-FBXL17
Method: X-RAY DIFFRACTION / Resolution: 3.21 Å

PDB-6w67:
The structure of S172A Keap1-BTB domain
Method: X-RAY DIFFRACTION / Resolution: 2.2 Å

PDB-6w68:
The structure of V98A S172A Keap1-BTB domain
Method: X-RAY DIFFRACTION / Resolution: 2.55 Å

PDB-6w69:
The structure of F64, S172A Keap1-BTB domain
Method: X-RAY DIFFRACTION / Resolution: 2.501 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsLIGASE/SIGNALING PROTEIN / E3 Ligase / Complex / BTB domain / LIGASE / LIGASE-SIGNALING PROTEIN complex / SIGNALING PROTEIN / ubiquitin / E3-ligase / multiprotein complex / substrate recognition

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