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Journal Article

Dual RING E3 architectures regulate multiubiquitination and ubiquitin chain elongation by APC/C.

MPS-Authors
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Dube,  P.
Research Group of 3D Electron Cryo-Microscopy, MPI for biophysical chemistry, Max Planck Society;

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Haselbach,  D.
Research Group of 3D Electron Cryo-Microscopy, MPI for Biophysical Chemistry, Max Planck Society;

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Stark,  H.
Department of Structural Dynamics, MPI for Biophysical Chemistry, Max Planck Society;

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2305964_Suppl_1.pdf
(Supplementary material), 456KB

2305964_Suppl_2.mp4
(Supplementary material), 12MB

2305964_Suppl_3.mp4
(Supplementary material), 22MB

2305964_Suppl_4.pdf
(Supplementary material), 10MB

Citation

Brown, N. G., VanderLinden, R., Watson, E. R., Weissmann, F., Ordureau, A., Wu, K. P., et al. (2016). Dual RING E3 architectures regulate multiubiquitination and ubiquitin chain elongation by APC/C. Cell, 165(6), 1440-1453. doi:10.1016/j.cell.2016.05.037.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-E4AF-4
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.