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Updated: Jun 26, 2026
11:13
Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Structural and mechanistic insights into Mps1 kinase activation
Wei Wang1, Yuting Yang2, Yuefeng Gao1
1Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Journal of Cellular and Molecular Medicine
|January 6, 2009
Summary
Mps1 kinase regulation is revealed through its unique inactive structure, showing how autophosphorylation and specific lysine residues control its activity during cell division and in response to spindle damage.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mps1 is a crucial kinase for the mitotic spindle assembly checkpoint.
- Mps1 activity is tightly regulated, increasing during mitosis and in response to spindle damage.
Purpose of the Study:
- To elucidate the molecular mechanisms regulating Mps1 kinase activity.
- To determine the crystal structure of the Mps1 kinase domain.
Main Methods:
- X-ray crystallography at 2.7-A resolution.
- Site-directed mutagenesis to identify key residues.
- Biochemical assays to assess kinase activity.
Main Results:
- The Mps1 kinase domain adopts a unique inactive conformation.
- Intramolecular interactions involving Glu residue and catalytic loop lock the inactive state.
- Autophosphorylation at T686 and T676 primes Mps1 for activation.
- Specific lysine residues are essential for substrate recruitment and activity.
Conclusions:
- Mps1 regulation involves a unique inactive conformation stabilized by intramolecular interactions.
- Autophosphorylation, particularly at T686, is critical for Mps1 activation.
- Key lysine residues facilitate substrate binding and maintain high kinase activity.
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