| Structural highlights
4fzf is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 4fza, 4fzd |
| Gene: | CAB39, MO25, CGI-66 (HUMAN), MST4, MASK (HUMAN) |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CAB39_HUMAN] Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1. [MST4_HUMAN] Mediator of cell growth. Modulates apoptosis.[1]
Publication Abstract from PubMed
Mammalian STE20-like kinase MST4 regulates multiple cellular aspects such as cell polarity and proliferation. MST4 acts downstream of LKB1/MO25/STRAD complex to induce brush border formation. MO25 directly interacts with MST4 to promote its kinase activity. Here, we report the crystal structure of MST4 in complex with MO25. Association of MO25 rotates the alphaC helix of MST4 toward its catalytic core, stabilizing the alphaC helix in an active position. The kinase domain of MST4 forms a specific homodimer that is required for trans-autophosphorylation. MO25-stimulated activation of MST4 promotes apoptosis in HEK293T cells. Atomic resolution permitted the study of interface mutations capable of disrupting the MST4-MO25 interaction or the kinase-domain-mediated homodimerization. These mutations impaired MST4 kinase activation and function within the cell. Collectively, our study identifies the activation mechanism of MST4 and provides a structural basis for further functional study.
Structure of the MST4 in Complex with MO25 Provides Insights into Its Activation Mechanism.,Shi Z, Jiao S, Zhang Z, Ma M, Zhang Z, Chen C, Wang K, Wang H, Wang W, Zhang L, Zhao Y, Zhou Z Structure. 2013 Feb 19. pii: S0969-2126(13)00014-2. doi:, 10.1016/j.str.2013.01.007. PMID:23434407[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D. PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Mol Biol Cell. 2007 Jun;18(6):1965-78. Epub 2007 Mar 14. PMID:17360971 doi:10.1091/mbc.E06-07-0608
- ↑ Shi Z, Jiao S, Zhang Z, Ma M, Zhang Z, Chen C, Wang K, Wang H, Wang W, Zhang L, Zhao Y, Zhou Z. Structure of the MST4 in Complex with MO25 Provides Insights into Its Activation Mechanism. Structure. 2013 Feb 19. pii: S0969-2126(13)00014-2. doi:, 10.1016/j.str.2013.01.007. PMID:23434407 doi:http://dx.doi.org/10.1016/j.str.2013.01.007
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