2M6N

3D solution structure of EMI1 (Early Mitotic Inhibitor 1)

2M6N の概要

• エントリーDOI: 10.2210/pdb2m6n/pdb
• 関連するPDBエントリー: 2CT7 2JMO
• NMR情報: BMRB: 19147
• 分子名称: F-box only protein 5, ZINC ION (2 entities in total)
• 機能のキーワード: emi1, apc, e3 ligase, zbr, cell cycle
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9UKT4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9736.18

構造登録者

Frye, J.J.,Brown, N.G.,Petzold, G.,Watson, E.R.,Royappa, G.R.,Nourse, A.,Jarvis, M.,Kriwacki, R.W.,Peters, J.,Stark, H.,Schulman, B.A. (登録日: 2013-04-06, 公開日: 2013-05-29, 最終更新日: 2024-05-01)

主引用文献

Frye, J.J.,Brown, N.G.,Petzold, G.,Watson, E.R.,Grace, C.R.,Nourse, A.,Jarvis, M.A.,Kriwacki, R.W.,Peters, J.M.,Stark, H.,Schulman, B.A.
Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal mechanism of E3 ligase shutdown.
Nat.Struct.Mol.Biol., 20:827-835, 2013

PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) is a ~1.5-MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell-cycle regulatory proteins. Inhibition of human APC/C(CDH1) during interphase by early mitotic inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and mitosis. Here, we report a hybrid structural approach involving NMR, electron microscopy and enzymology, which reveal that EMI1's 143-residue C-terminal domain inhibits multiple APC/C(CDH1) functions. The intrinsically disordered D-box, linker and tail elements, together with a structured zinc-binding domain, bind distinct regions of APC/C(CDH1) to synergistically both block the substrate-binding site and inhibit ubiquitin-chain elongation. The functional importance of intrinsic structural disorder is explained by enabling a small inhibitory domain to bind multiple sites to shut down various functions of a 'molecular machine' nearly 100 times its size.

PubMed: 23708605
DOI: 10.1038/nsmb.2593

実験手法

SOLUTION NMR