@article{f5b638f3c3fc4be58f7b4b9033f2f838,
title = "Structure of the MST4 in complex with MO25 provides insights into its activation mechanism",
abstract = "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 αC helix of MST4 toward its catalytic core, stabilizing the αC 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.",
author = "Zhubing Shi and Shi Jiao and Zhen Zhang and Miao Ma and Zhao Zhang and Cuicui Chen and Ke Wang and Huizhen Wang and Wenjia Wang and Lei Zhang and Yun Zhao and Zhaocai Zhou",
note = "Funding Information: We thank the staff at beamline BL17U of the Shanghai Synchrotron Radiation Facility (SSRF) for help with data collection. Special thanks go to Dr. Mark I. Greene at the University of Pennsylvania and Dr. Dangsheng Li at the Shanghai Information Center for Life Sciences for their critical reading of the manuscript. This work was supported by the 973 program of the Ministry of Science and Technology of China (2010CB529701, 2012CB910204, 2010CB912101, and 2011CB943902), the National Natural Science Foundation of China (31270808, 30970566, 10979005, 30971647, and 31171414), the Science and Technology Commission of Shanghai Municipality (11JC14140000), and the “Strategic Priority Research Program” of the Chinese Academy of Sciences (XDA01010405). Y.Z. and Z.Z. are scholars of the Hundred Talents Program of the Chinese Academy of Sciences. ",
year = "2013",
month = mar,
day = "5",
doi = "10.1016/j.str.2013.01.007",
language = "English (US)",
volume = "21",
pages = "449--461",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "3",
}