4B94

Crystal structure of human Mps1 TPR domain

4B94 の概要

• エントリーDOI: 10.2210/pdb4b94/pdb
• 関連するPDBエントリー: 2X9E
• 分子名称: DUAL SPECIFICITY PROTEIN KINASE TTK, TETRAETHYLENE GLYCOL, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: transferase, kinetochore, mitosis
• 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: 83192.49

構造登録者

Littler, D.,von Castelmur, E.,De Marco, V.,Perrakis, A. (登録日: 2012-08-31, 公開日: 2013-04-24, 最終更新日: 2024-05-08)

主引用文献

Nijenhuis, W.,von Castelmur, E.,Littler, D.,De Marco, V.,Tromer, E.,Vleugel, M.,van Osch, M.H.,Snel, B.,Perrakis, A.,Kops, G.J.
A Tpr Domain-Containing N-Terminal Module of Mps1 is Required for its Kinetochore Localization by Aurora B.
J.Cell Biol., 201:217-, 2013

PubMed Abstract: The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B-dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization.

PubMed: 23569217
DOI: 10.1083/JCB.201210033

実験手法

X-RAY DIFFRACTION (2.2 Å)