4FZD

Crystal structure of MST4-MO25 complex with WSF motif

Summary for 4FZD

• Entry DOI: 10.2210/pdb4fzd/pdb
• Related: 4FZA 4FZF
• Descriptor: Calcium-binding protein 39, Serine/threonine-protein kinase MST4, C-terminal peptide from Serine/threonine-protein kinase MST4, ... (5 entities in total)
• Functional Keywords: scaffold protein, protein ser/thr kinase, atp binding, signaling protein-transferase complex, signaling protein/transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (Potential): Q9Y376; Cytoplasm: Q9P289 Q9P289
• Total number of polymer chains: 3
• Total formula weight: 71002.56

Authors

Shi, Z.B.,Zhou, Z.C. (deposition date: 2012-07-06, release date: 2013-03-06, Last modification date: 2023-11-08)

Primary citation

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, 21:449-461, 2013

PubMed 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.

PubMed: 23434407
DOI: 10.1016/j.str.2013.01.007

Experimental method

X-RAY DIFFRACTION (3.25 Å)