6CZO

The KNL1-PP1 Holoenzyme

6CZO の概要

• エントリーDOI: 10.2210/pdb6czo/pdb
• 分子名称: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, CASC5 protein, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: phosphatase, regulator, slim, kinetochore, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82631.89

構造登録者

Bajaj, R.,Peti, W.,Page, R. (登録日: 2018-04-09, 公開日: 2019-01-23, 最終更新日: 2023-10-04)

主引用文献

Bajaj, R.,Bollen, M.,Peti, W.,Page, R.
KNL1 Binding to PP1 and Microtubules Is Mutually Exclusive.
Structure, 26:1327-1336.e4, 2018

PubMed Abstract: The kinetochore scaffold 1 (KNL1) protein coordinates the spindle assembly checkpoint (SAC), a signaling pathway that delays chromosome segregation until all sister chromatids are properly attached to spindle microtubules. Recently, microtubules and protein phosphatase 1 (PP1), which both bind the N-terminal domain of KNL1, have emerged as regulators of the SAC; however, how these proteins interact to contribute to SAC signaling is unknown. Here, we use X-ray crystallography, nuclear magnetic resonance spectroscopy, and biochemical assays to show how KNL1 binds both PP1 and microtubules. Unexpectedly, we discovered that PP1 and microtubules bind KNL1 via overlapping binding sites. Further, we showed that Aurora B kinase phosphorylation results in distinct patterns of KNL1 complex disruption. Finally, combining this data with co-sedimentation assays unequivocally demonstrated that microtubules and PP1 binding to KNL1 is mutually exclusive, with preferential formation of the KNL1:PP1 holoenzyme in the presence of PP1.

PubMed: 30100357
DOI: 10.1016/j.str.2018.06.013

実験手法

X-RAY DIFFRACTION (2.95 Å)