4b94

Crystal structure of human Mps1 TPR domain

spinqualitylabelsall models 4b94, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4b94 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MLI, PEG, PG4, PGE Related: 2x9e Activity: Dual-specificity kinase, with EC number 2.7.12.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TTK_HUMAN] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint. Publication Abstract from PubMed 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. A TPR domain-containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B.,Nijenhuis W, von Castelmur E, Littler D, De Marco V, Tromer E, Vleugel M, van Osch MH, Snel B, Perrakis A, Kops GJ J Cell Biol. 2013 Apr 15;201(2):217-31. doi: 10.1083/jcb.201210033. Epub 2013 Apr, 8. PMID:23569217 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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