4RG6

Crystal structure of APC3-APC16 complex

4RG6 の概要

• エントリーDOI: 10.2210/pdb4rg6/pdb
• 関連するPDBエントリー: 4RG7 4RG9
• 分子名称: Cell division cycle protein 27 homolog, Anaphase-promoting complex subunit 16 (2 entities in total)
• 機能のキーワード: asymmetric complex, tpr fplding, protein assembly, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P30260; Cytoplasm : Q96DE5
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 132862.14

構造登録者

Yamaguchi, M.,Yu, S.,Miller, D.J.,Schulman, B.A. (登録日: 2014-09-29, 公開日: 2014-12-24, 最終更新日: 2024-02-28)

主引用文献

Yamaguchi, M.,Yu, S.,Qiao, R.,Weissmann, F.,Miller, D.J.,VanderLinden, R.,Brown, N.G.,Frye, J.J.,Peters, J.M.,Schulman, B.A.
Structure of an APC3-APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome.
J.Mol.Biol., 427:1748-1764, 2015

PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) is a massive E3 ligase that controls mitosis by catalyzing ubiquitination of key cell cycle regulatory proteins. The APC/C assembly contains two subcomplexes: the "Platform" centers around a cullin-RING-like E3 ligase catalytic core; the "Arc Lamp" is a hub that mediates transient association with regulators and ubiquitination substrates. The Arc Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) proteins (APC7, APC3, APC6, and APC8) that homodimerize and stack with quasi-2-fold symmetry. Within the APC/C complex, APC3 serves as center for regulation. APC3's TPR motifs recruit substrate-binding coactivators, CDC20 and CDH1, via their C-terminal conserved Ile-Arg (IR) tail sequences. Human APC3 also binds APC16 and APC7 and contains a >200-residue loop that is heavily phosphorylated during mitosis, although the basis for APC3 interactions and whether loop phosphorylation is required for ubiquitination are unclear. Here, we map the basis for human APC3 assembly with APC16 and APC7, report crystal structures of APC3Δloop alone and in complex with the C-terminal domain of APC16, and test roles of APC3's loop and IR tail binding surfaces in APC/C-catalyzed ubiquitination. The structures show how one APC16 binds asymmetrically to the symmetric APC3 dimer and, together with biochemistry and prior data, explain how APC16 recruits APC7 to APC3, show how APC3's C-terminal domain is rearranged in the full APC/C assembly, and visualize residues in the IR tail binding cleft important for coactivator-dependent ubiquitination. Overall, the results provide insights into assembly, regulation, and interactions of TPR proteins and the APC/C.

PubMed: 25490258
DOI: 10.1016/j.jmb.2014.11.020

実験手法

X-RAY DIFFRACTION (3.3 Å)