Structural and mechanistic insights into Mps1 kinase activation.

Journal of Cellular and Molecular Medicine
Wei WangXuedong Liu

Abstract

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-A-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation. Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the...Continue Reading

References

Jun 1, 1992·Molecular and Cellular Biology·E M DouvilleJ C Bell
Aug 9, 1991·Cell·R Li, A W Murray
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 11, 1999·Current Opinion in Genetics & Development·A Amon
Feb 13, 2001·Current Opinion in Genetics & Development·K Wassmann, R Benezra
May 23, 2002·Cell·Morgan Huse, John Kuriyan
Sep 6, 2002·Oncogene·Mark Winey, Brenda J Huneycutt
Dec 11, 2002·Current Opinion in Cell Biology·Hongtao Yu
Mar 26, 2003·Cell·Stephen C Harrison
Apr 11, 2003·Molecular Biology of the Cell·Song-Tao LiuTim J Yen
Jul 12, 2003·Nature Cell Biology·Eunah Chung, Rey-Huei Chen
Feb 14, 2004·Cell Cycle·Harold A FiskMark Winey
Jun 16, 2004·Current Opinion in Genetics & Development·Viji M DraviamPeter K Sorger
Jul 3, 2004·Genes & Development·Kenneth D PossMark T Keating
May 17, 2005·Structure·Ming LeiStephen C Harrison
Oct 1, 2005·Nature Reviews. Cancer·Geert J P L KopsDon W Cleveland
Apr 25, 2007·The Journal of Biological Chemistry·Songcheng ZhuXuedong Liu
Aug 31, 2007·The Journal of Biological Chemistry·Christopher P MattisonMark Winey
Dec 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jungseog KangHongtao Yu
May 16, 2008·The Journal of Biological Chemistry·Matthew L H ChuLydia Tabernero
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

❮ Previous
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Citations

Jun 19, 2013·Chromosoma·Anna-Leena Salmela, Marko J Kallio
Apr 13, 2010·Nature Chemical Biology·Nicholas KwiatkowskiNathanael S Gray
Oct 5, 2010·The Journal of Biological Chemistry·Tingting SunXuedong Liu
May 4, 2012·Molecular Biology of the Cell·Friederike AlthoffChristian F Lehner
Dec 12, 2012·Open Biology·Richard BaylissSharon Yeoh
Oct 11, 2012·PloS One·Eduardo Alves Gamosa de OliveiraMarco Antônio Lopes Cruz
Apr 10, 2012·Annual Review of Biochemistry·Xuedong Liu, Mark Winey
Sep 12, 2015·Molecular Biology of the Cell·Dwitiya B SawantHarold A Fisk
Jan 17, 2012·Current Biology : CB·Violeta MorinAriane Abrieu
Feb 21, 2018·Frontiers in Cell and Developmental Biology·Julie P I Welburn, A Arockia Jeyaprakash
Feb 10, 2019·Biomolecules·Margarida Moura, Carlos Conde
Dec 18, 2015·Oncotarget·Agnese RestucciaWei Dai
Aug 17, 2018·Open Biology·Spyridon T Pachis, Geert J P L Kops
Apr 4, 2021·Cell Metabolism·Liwen ZhangPengcheng Bu
Jan 27, 2010·Biochemistry·Matthew L H ChuPatrick A Eyers
May 26, 2021·Cell Death & Disease·Qiang FangFeng Sun

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