Structural basis for dimerization quality control
| Autor: | Predrag Jevtić, Brandon G. Lew, John Kuriyan, Christine L. Gee, Michael Rape, Elijah L. Mena, Eva Nogales, David Akopian, Basil J. Greber |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Protein Folding General Science & Technology Plasma protein binding FBXL17 Models Biological Article 03 medical and health sciences 0302 clinical medicine Protein stability Ubiquitin Models Wrap around ubiquitin Humans BTB domain quality control 030304 developmental biology 0303 health sciences Stem Cell Factor Multidisciplinary dimerization Kelch-Like ECH-Associated Protein 1 biology Extramural Chemistry Protein Stability F-Box Proteins Ubiquitination Molecular Biological Ubiquitin ligase KEAP1 Proteostasis domain swap BTB-POZ Domain biology.protein Biophysics Protein folding Protein Multimerization 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Nature, vol 586, iss 7829 Nature |
| Popis: | 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 helpsto 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. |
| Databáze: | OpenAIRE |
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