1GO4

Crystal structure of Mad1-Mad2 reveals a conserved Mad2 binding motif in Mad1 and Cdc20.

1GO4 の概要

• エントリーDOI: 10.2210/pdb1go4/pdb
• 関連するPDBエントリー: 1DUJ
• 分子名称: Mitotic spindle assembly checkpoint protein MAD2A, Mitotic spindle assembly checkpoint protein MAD1 (3 entities in total)
• 機能のキーワード: mitotic spindle checkpoint, cell cycle, mitosis, nuclear pro
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 140563.48

構造登録者

Sironi, L.,Mapelli, M.,Jeang, K.T.,Musacchio, A. (登録日: 2001-10-17, 公開日: 2002-05-16, 最終更新日: 2023-12-13)

主引用文献

Sironi, L.,Mapelli, M.,Knapp, S.,De Antoni, A.,Jeang, K.T.,Musacchio, A.
Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a 'safety belt' binding mechanism for the spindle checkpoint.
EMBO J., 21:2496-2506, 2002

PubMed Abstract: The spindle checkpoint protein Mad1 recruits Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. The crystal structure of the Mad1-Mad2 complex reveals an asymmetric tetramer, with elongated Mad1 monomers parting from a coiled-coil to form two connected sub-complexes with Mad2. The Mad2 C-terminal tails are hinged mobile elements wrapping around the elongated ligands like molecular 'safety belts'. We show that Mad1 is a competitive inhibitor of the Mad2-Cdc20 complex, and propose that the Mad1-Mad2 complex acts as a regulated gate to control Mad2 release for Cdc20 binding. Mad1-Mad2 is strongly stabilized in the tetramer, but a 1:1 Mad1-Mad2 complex slowly releases Mad2 for Cdc20 binding, driven by favourable binding energies. Thus, the rate of Mad2 binding to Cdc20 during checkpoint activation may be regulated by conformational changes that destabilize the tetrameric Mad1-Mad2 assembly to promote Mad2 release. We also show that unlocking the Mad2 C-terminal tail is required for ligand release from Mad2, and that the 'safety belt' mechanism may prolong the lifetime of Mad2-ligand complexes.

PubMed: 12006501
DOI: 10.1093/emboj/21.10.2496

実験手法

X-RAY DIFFRACTION (2.05 Å)