6W66

The structure of the F64A, S172A mutant Keap1-BTB domain in complex with SKP1-FBXL17

Summary for 6W66

• Entry DOI: 10.2210/pdb6w66/pdb
• Descriptor: S-phase kinase-associated protein 1, F-box/LRR-repeat protein 17, Kelch-like ECH-associated protein 1 (3 entities in total)
• Functional Keywords: e3 ligase, complex, btb domain, ligase, ligase-signaling protein complex, ligase/signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 78511.14

Authors

Mena, E.L.,Gee, C.L.,Kuriyan, J.,Rape, M. (deposition date: 2020-03-16, release date: 2020-08-19, Last modification date: 2023-10-18)

Primary citation

Mena, E.L.,Jevtic, P.,Greber, B.J.,Gee, C.L.,Lew, B.G.,Akopian, D.,Nogales, E.,Kuriyan, J.,Rape, M.
Structural basis for dimerization quality control.
Nature, 586:452-456, 2020

PubMed Abstract: 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.

PubMed: 32814905
DOI: 10.1038/s41586-020-2636-7

Experimental method

X-RAY DIFFRACTION (3.21 Å)