6w69

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The structure of F64, S172A Keap1-BTB domainThe structure of F64, S172A Keap1-BTB domain

Structural highlights

6w69 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.501Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KEAP1_HUMAN

Publication Abstract from PubMed

Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration(1). Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition(2), 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 beta-sheet around a highly divergent beta-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.

Structural basis for dimerization quality control.,Mena EL, Jevtic P, Greber BJ, Gee CL, Lew BG, Akopian D, Nogales E, Kuriyan J, Rape M Nature. 2020 Aug 19. pii: 10.1038/s41586-020-2636-7. doi:, 10.1038/s41586-020-2636-7. PMID:32814905[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Mena EL, Jevtic P, Greber BJ, Gee CL, Lew BG, Akopian D, Nogales E, Kuriyan J, Rape M. Structural basis for dimerization quality control. Nature. 2020 Aug 19. pii: 10.1038/s41586-020-2636-7. doi:, 10.1038/s41586-020-2636-7. PMID:32814905 doi:http://dx.doi.org/10.1038/s41586-020-2636-7

6w69, resolution 2.50Å

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OCA