Structural highlights
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.[1]
Publication Abstract from PubMed
Monopolar spindle 1 (Mps1) is a dual-specificity protein kinase, orchestrating faithful chromosome segregation during mitosis. All reported structures of the Mps1 kinase adopt the hallmarks of an inactive conformation, which includes a mostly disordered activation loop. Here we present a 2.4A resolution crystal structure of an 'extended' version of the Mps1 kinase domain, which shows an ordered activation loop. However, the other structural characteristics of an active kinase are not present. Our structure shows that the Mps1 activation loop can fit to the ATP binding pocket and interferes with ATP, but less so with inhibitors binding, partly explain the potency of various Mps1 inhibitors. This article is protected by copyright. All rights reserved.
A crystal structure of the human protein kinase Mps1 reveals an ordered conformation of the activation loop.,Roorda JC, Joosten RP, Perrakis A, Hiruma Y Proteins. 2018 Dec 23. doi: 10.1002/prot.25651. PMID:30582207[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. PMID:18243099 doi:10.1016/j.cell.2007.11.046
- ↑ Roorda JC, Joosten RP, Perrakis A, Hiruma Y. A crystal structure of the human protein kinase Mps1 reveals an ordered conformation of the activation loop. Proteins. 2018 Dec 23. doi: 10.1002/prot.25651. PMID:30582207 doi:http://dx.doi.org/10.1002/prot.25651
