positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / positive regulation of synaptic plasticity / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process ...positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / positive regulation of synaptic plasticity / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / metaphase/anaphase transition of mitotic cell cycle / protein branched polyubiquitination / Phosphorylation of the APC/C / regulation of exit from mitosis / positive regulation of dendrite morphogenesis / positive regulation of mitotic metaphase/anaphase transition / protein K11-linked ubiquitination / regulation of mitotic metaphase/anaphase transition / ubiquitin-ubiquitin ligase activity / mitotic metaphase chromosome alignment / Regulation of APC/C activators between G1/S and early anaphase / Transcriptional Regulation by VENTX / cullin family protein binding / enzyme-substrate adaptor activity / positive regulation of axon extension / protein K48-linked ubiquitination / heterochromatin / intercellular bridge / APC/C:Cdc20 mediated degradation of Cyclin B / nuclear periphery / regulation of mitotic cell cycle / APC-Cdc20 mediated degradation of Nek2A / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / G protein-coupled receptor binding / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / brain development / kinetochore / CDK-mediated phosphorylation and removal of Cdc6 / spindle / neuron projection development / ubiquitin-protein transferase activity / mitotic spindle / ubiquitin protein ligase activity / Separation of Sister Chromatids / nervous system development / Antigen processing: Ubiquitination & Proteasome degradation / mitotic cell cycle / microtubule cytoskeleton / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / cell differentiation / protein ubiquitination / negative regulation of gene expression / cell division / intracellular membrane-bounded organelle / ubiquitin protein ligase binding / centrosome / nucleolus / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2024 タイトル: Cryo-EM structures of apo-APC/C and APC/C complexes provide insights into APC/C regulation. 著者: Anna Höfler / Jun Yu / Jing Yang / Ziguo Zhang / Leifu Chang / Stephen H McLaughlin / Geoffrey W Grime / Elspeth F Garman / Andreas Boland / David Barford / 要旨: APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle ...APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle regulatory proteins for degradation. The APC/C itself is regulated by the sequential action of its coactivator subunits CDC20 and CDH1, post-translational modifications, and its inhibitory binding partners EMI1 and the mitotic checkpoint complex. In this study, we took advantage of developments in cryo-electron microscopy to determine the structures of human APC/C and apo-APC/C at 2.9 Å and 3.2 Å resolution, respectively, providing insights into the regulation of APC/C activity. The high-resolution maps allow the unambiguous assignment of an α-helix to the N-terminus of CDH1 (CDH1) in the APC/C ternary complex. We also identify a zinc-binding module in APC2 that confers structural stability to the complex, and we confirm the presence of zinc ions experimentally. Finally, due to the higher resolution and well defined density of these maps, we are able to build, aided by AlphaFold predictions, several intrinsically disordered regions in different APC/C subunits that likely play a role in proper APC/C assembly and regulation of its activity.