1S2H

The Mad2 spindle checkpoint protein possesses two distinct natively folded states

1S2H の概要

• エントリーDOI: 10.2210/pdb1s2h/pdb
• 関連するPDBエントリー: 1DUJ 1KLQ
• 分子名称: Mitotic spindle assembly checkpoint protein MAD2A (1 entity in total)
• 機能のキーワード: mad2, spindle checkpoint protein, cell cycle
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q13257
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23504.82

構造登録者

Luo, X.,Tang, Z.,Xia, G.,Wassmann, K.,Matsumoto, T.,Rizo, J.,Yu, H. (登録日: 2004-01-08, 公開日: 2004-03-30, 最終更新日: 2024-05-22)

主引用文献

Luo, X.,Tang, Z.,Xia, G.,Wassmann, K.,Matsumoto, T.,Rizo, J.,Yu, H.
The Mad2 spindle checkpoint protein has two distinct natively folded states.
Nat.Struct.Mol.Biol., 11:338-345, 2004

PubMed Abstract: The spindle checkpoint delays chromosome segregation in response to misaligned sister chromatids during mitosis, thus ensuring the fidelity of chromosome inheritance. Through binding to Cdc20, the Mad2 spindle checkpoint protein inhibits the target of this checkpoint, the ubiquitin protein ligase APC/C(Cdc20). We now show that without cofactor binding or covalent modification Mad2 adopts two distinct folded conformations at equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C inhibition. Overexpression of a Mad2 mutant that specifically sequesters N2-Mad2 partially blocks checkpoint signaling in living cells. The two Mad2 conformers interconvert slowly in vitro, but interconversion is accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our results suggest that the unusual two-state behavior of Mad2 is critical for spindle checkpoint signaling.

PubMed: 15024386
DOI: 10.1038/nsmb748

実験手法

SOLUTION NMR