6akk | pdb_00006akk

Crystal structure of the second Coiled-coil domain of SIKE1

spinqualitylabelsall models 6akk, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6akk 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: GOL Gene: SIKE1, SIKE (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SIKE1_HUMAN] Physiological suppressor of IKK-epsilon and TBK1 that plays an inhibitory role in virus- and TLR3-triggered IRF3. Inhibits TLR3-mediated activation of interferon-stimulated response elements (ISRE) and the IFN-beta promoter. May act by disrupting the interactions of IKBKE or TBK1 with TICAM1/TRIF, IRF3 and DDX58/RIG-I. Does not inhibit NF-kappa-B activation pathways. Publication Abstract from PubMed Striatin-interacting phosphatases and kinases (STRIPAKs) are evolutionarily conserved supramolecular complexes, which have been implicated in the Hippo signaling pathway. Yet the topological structure and dynamic assembly of STRIPAK complexes remain elusive. Here, we report the overall architecture and substructures of a Hippo kinase-containing STRIPAK complex. PP2Aa/c-bound STRN3 directly contacts the Hippo kinase MST2 and also controls the loading of MST2 via two "arms" in a phosphorylation-dependent manner, one arm being STRIP1 and the other SIKE1-SLMAP. A decreased cell density triggered the dissociation of the STRIP1 arm from STRIPAK, reflecting the dynamic assembly of the complex upon sensing upstream signals. Crystallographic studies defined at atomic resolution the interface between STRN3 and SIKE1, and that between SIKE1 and SLMAP. Disrupting the complex assembly abrogated the regulatory effect of STRIPAK towards Hippo signaling. Collectively, our study revealed a "two-arm" assembly of STRIPAK with context-dependent dynamics, offering a framework for further studies on Hippo signaling and biological processes involving MST kinases. Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling.,Tang Y, Chen M, Zhou L, Ma J, Li Y, Zhang H, Shi Z, Xu Q, Zhang X, Gao Z, Zhao Y, Cheng Y, Jiao S, Zhou Z Cell Discov. 2019 Jan 8;5:3. doi: 10.1038/s41421-018-0077-3. eCollection 2019. PMID:30622739 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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