| Structural highlights
Function
CDC16_HUMAN Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.[1]
Publication Abstract from PubMed
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.
Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C.,Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA Cell. 2016 Jun 2;165(6):1440-53. doi: 10.1016/j.cell.2016.05.037. PMID:27259151[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
- ↑ Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA. Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. Cell. 2016 Jun 2;165(6):1440-53. doi: 10.1016/j.cell.2016.05.037. PMID:27259151 doi:http://dx.doi.org/10.1016/j.cell.2016.05.037
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