4GGD

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.

4GGD の概要

• エントリーDOI: 10.2210/pdb4ggd/pdb
• 関連するPDBエントリー: 4GGA 4GGC
• 分子名称: Cell division cycle protein 20 homolog, Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (3 entities in total)
• 機能のキーワード: cell cycle, mitosis, securin, ubiquitination, wd40
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q12834; Cytoplasm: O60566
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100512.73

構造登録者

Luo, X.,Tian, W.,Tomchick, D.R. (登録日: 2012-08-06, 公開日: 2012-11-07, 最終更新日: 2024-02-28)

主引用文献

Tian, W.,Li, B.,Warrington, R.,Tomchick, D.R.,Yu, H.,Luo, X.
Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.
Proc.Natl.Acad.Sci.USA, 109:18419-18424, 2012

PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. The mitotic APC/C activator, the cell division cycle 20 (Cdc20) protein, directly interacts with APC/C degrons--the destruction (D) and KEN boxes. APC/C(Cdc20) is the target of the spindle checkpoint. Checkpoint inhibition of APC/C(Cdc20) requires the binding of a BubR1 KEN box to Cdc20. How APC/C recognizes substrates is not understood. We report the crystal structures of human Cdc20 alone or bound to a BubR1 KEN box. Cdc20 has a disordered N-terminal region and a C-terminal WD40 β propeller with a preformed KEN-box-binding site at its top face. We identify a second conserved surface at the side of the Cdc20 β propeller as a D-box-binding site. The D box of securin, but not its KEN box, is critical for securin ubiquitination by APC/C(Cdc20). Although both motifs contribute to securin ubiquitination by APC/C(Cdh1), securin mutants lacking either motif are efficiently ubiquitinated. Furthermore, D-box peptides diminish the ubiquitination of KEN-box substrates by APC/C(Cdh1), suggesting possible competition between the two motifs. Our results indicate the lack of strong positive cooperativity between the two degrons of securin. We propose that low-cooperativity, multisite target recognition enables APC/C to robustly ubiquitinate diverse substrates and helps to drive cell cycle oscillations.

PubMed: 23091007
DOI: 10.1073/pnas.1213438109

実験手法

X-RAY DIFFRACTION (2.435 Å)