6AO5
Crystal structure of human MST2 in complex with SAV1 SARAH domain
Summary for 6AO5
| Entry DOI | 10.2210/pdb6ao5/pdb |
| Descriptor | Serine/threonine-protein kinase 3, Protein salvador homolog 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total) |
| Functional Keywords | hippo, mst autoactivation, dimerization, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Cytoplasm : Q13188 Nucleus : Q9H4B6 |
| Total number of polymer chains | 2 |
| Total formula weight | 53535.43 |
| Authors | Tomchick, D.R.,Luo, X.,Ni, L. (deposition date: 2017-08-15, release date: 2017-11-08, Last modification date: 2023-10-04) |
| Primary citation | Bae, S.J.,Ni, L.,Osinski, A.,Tomchick, D.R.,Brautigam, C.A.,Luo, X. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. Elife, 6:-, 2017 Cited by PubMed Abstract: The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAK as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1-MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAK PP2A phosphatase complex. PubMed: 29063833DOI: 10.7554/eLife.30278 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.955 Å) |
Structure validation
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