4H7Y
Crystal structure of the tetratricopeptide repeat (TPR) motif of human dual specificity protein kinase Mps1
Summary for 4H7Y
| Entry DOI | 10.2210/pdb4h7y/pdb |
| Related | 4H7X |
| Descriptor | Dual specificity protein kinase TTK (2 entities in total) |
| Functional Keywords | mitotic checkpoint kinase, chromosome instability, cancer, tetratricopeptide repeat (tpr) motif, mitotic checkpoint, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 72748.22 |
| Authors | Bolanos-Garcia, V.M.,Chirgadze, D.Y.,Blundell, T.L. (deposition date: 2012-09-21, release date: 2012-12-12, Last modification date: 2024-02-28) |
| Primary citation | 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 Cited by 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: 23067341DOI: 10.1042/BJ20121448 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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