6ar2

Structure of human SLMAP FHA domain in complex with pMST2

spinqualitylabelsall models 6ar2, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ar2 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SLMAP_HUMAN Brugada syndrome. Function SLMAP_HUMAN May play a role during myoblast fusion. Publication Abstract from PubMed 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 STRIPAKSLMAP 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 STRIPAKSLMAP PP2A phosphatase complex. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK.,Bae SJ, Ni L, Osinski A, Tomchick DR, Brautigam CA, Luo X Elife. 2017 Oct 24;6. pii: e30278. doi: 10.7554/eLife.30278. PMID:29063833 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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