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| | ==Crystal structure of SLMAP-SIKE1 complex== | | ==Crystal structure of SLMAP-SIKE1 complex== |
| - | <StructureSection load='6akm' size='340' side='right' caption='[[6akm]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='6akm' size='340' side='right'caption='[[6akm]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6akm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AKM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6akm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AKM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIKE1, SIKE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SLMAP, KIAA1601, SLAP, UNQ1847/PRO3577 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6akm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6akm OCA], [http://pdbe.org/6akm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6akm RCSB], [http://www.ebi.ac.uk/pdbsum/6akm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6akm ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6akm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6akm OCA], [https://pdbe.org/6akm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6akm RCSB], [https://www.ebi.ac.uk/pdbsum/6akm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6akm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/SLMAP_HUMAN SLMAP_HUMAN]] Brugada syndrome. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SIKE1_HUMAN 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.<ref>PMID:16281057</ref> [[http://www.uniprot.org/uniprot/SLMAP_HUMAN SLMAP_HUMAN]] May play a role during myoblast fusion. | + | [https://www.uniprot.org/uniprot/SIKE1_HUMAN 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.<ref>PMID:16281057</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Ma, J]] | + | [[Category: Chen M]] |
| - | [[Category: Zhou, Z C]] | + | [[Category: Ma J]] |
| - | [[Category: Coiled-coil domain]] | + | [[Category: Zhou ZC]] |
| - | [[Category: Heterotetramer]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang J, Liu T, Xu LG, Chen D, Zhai Z, Shu HB. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. EMBO J. 2005 Dec 7;24(23):4018-28. doi: 10.1038/sj.emboj.7600863. Epub 2005 Nov, 10. PMID:16281057 doi:http://dx.doi.org/10.1038/sj.emboj.7600863
- ↑ 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. Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling. Cell Discov. 2019 Jan 8;5:3. doi: 10.1038/s41421-018-0077-3. eCollection 2019. PMID:30622739 doi:http://dx.doi.org/10.1038/s41421-018-0077-3
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