Structural basis for dimerization quality control

Mena, Elijah L.; Jevtić, Predrag; Greber, Basil J.; Gee, Christine L.; Lew, Brandon G.; Akopian, David; Nogales, Eva; Kuriyan, John; Rape, Michael

doi:10.1038/s41586-020-2636-7

Structural basis for dimerization quality control

Journal Article · Wed Aug 19 00:00:00 UTC 2020 · Nature (London)

DOI:https://doi.org/10.1038/s41586-020-2636-7· OSTI ID:1838323

^[1]; Jevtić, Predrag ^[2]; ^[3]; ^[2]; Lew, Brandon G. ^[2]; Akopian, David ^[1]; ^[4]; Kuriyan, John ^[4]; ^[5]

Univ. of California, Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.
Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences (QB3); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences (QB3); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences (QB3)

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. Furthermore, 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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS); USDOE; University of California

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1838323

Journal Information:: Nature (London), Journal Name: Nature (London) Journal Issue: 7829 Vol. 586; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Enzyme mechanisms
Protein quality control
Structure determination
Ubiquitylation

Structural basis for dimerization quality control

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References (48)

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