4H7Y

Crystal structure of the tetratricopeptide repeat (TPR) motif of human dual specificity protein kinase Mps1

4H7Y の概要

• エントリーDOI: 10.2210/pdb4h7y/pdb
• 関連するPDBエントリー: 4H7X
• 分子名称: Dual specificity protein kinase TTK (2 entities in total)
• 機能のキーワード: mitotic checkpoint kinase, chromosome instability, cancer, tetratricopeptide repeat (tpr) motif, mitotic checkpoint, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 72748.22

構造登録者

Bolanos-Garcia, V.M.,Chirgadze, D.Y.,Blundell, T.L. (登録日: 2012-09-21, 公開日: 2012-12-12, 最終更新日: 2024-02-28)

主引用文献

Thebault, P.,Chirgadze, D.Y.,Dou, Z.,Blundell, T.L.,Elowe, S.,Bolanos-Garcia, V.M.
Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint).
Biochem.J., 448:321-328, 2012

PubMed Abstract: The SAC (spindle assembly checkpoint) is a surveillance system that ensures the timely and accurate transmission of the genetic material to offspring. The process implies kinetochore targeting of the mitotic kinases Bub1 (budding uninhibited by benzamidine 1), BubR1 (Bub1 related) and Mps1 (monopolar spindle 1), which is mediated by the N-terminus of each kinase. In the present study we report the 1.8 Å (1 Å=0.1 nm) crystal structure of the TPR (tetratricopeptide repeat) domain in the N-terminal region of human Mps1. The structure reveals an overall high similarity to the TPR motif of the mitotic checkpoint kinases Bub1 and BubR1, and a number of unique features that include the absence of the binding site for the kinetochore structural component KNL1 (kinetochore-null 1; blinkin), and determinants of dimerization. Moreover, we show that a stretch of amino acids at the very N-terminus of Mps1 is required for dimer formation, and that interfering with dimerization results in mislocalization and misregulation of kinase activity. The results of the present study provide an important insight into the molecular details of the mitotic functions of Mps1 including features that dictate substrate selectivity and kinetochore docking.

PubMed: 23067341
DOI: 10.1042/BJ20121448

実験手法

X-RAY DIFFRACTION (1.8 Å)