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Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C
- Source :
- Cell
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination.
- Subjects :
- Models, Molecular
0301 basic medicine
Saccharomyces cerevisiae Proteins
macromolecular substances
Ubiquitin-conjugating enzyme
Ring (chemistry)
Bioinformatics
Anaphase-Promoting Complex-Cyclosome
Article
General Biochemistry, Genetics and Molecular Biology
Structure-Activity Relationship
03 medical and health sciences
0302 clinical medicine
Ubiquitin
Chain (algebraic topology)
Humans
Structure–activity relationship
Amino Acid Sequence
Peptide sequence
biology
Biochemistry, Genetics and Molecular Biology(all)
Cryoelectron Microscopy
Ubiquitination
Protein ubiquitination
Cell biology
030104 developmental biology
Ubiquitin-Conjugating Enzymes
Biocatalysis
biology.protein
030217 neurology & neurosurgery
Cullin
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 165
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....998aa546295d929e0d1527b5e5199d17