4jlc

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{{STRUCTURE_4jlc| PDB=4jlc | SCENE= }}
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==Crystal structure of mouse TBK1 bound to SU6668==
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===Crystal structure of mouse TBK1 bound to SU6668===
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<StructureSection load='4jlc' size='340' side='right' caption='[[4jlc]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23746807}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4jlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JLC FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SU6:3-{2,4-DIMETHYL-5-[(Z)-(2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL]-1H-PYRROL-3-YL}PROPANOIC+ACID'>SU6</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jl9|4jl9]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tbk1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<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=4jlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jlc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jlc RCSB], [http://www.ebi.ac.uk/pdbsum/4jlc PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Tank-binding kinase 1 (TBK1) is a serine/threonine protein-kinase mediating innate antimicrobial immunity. TBK1 is involved in the signaling of TLRs, RLRs, and STING-mediated sensing of cytosolic DNA. Stimulation of these receptors results in the activation of TBK1, which phosphorylates interferon regulatory factor (IRF)-3. Phosphorylated IRF-3 translocates into the nucleus to initiate the transcription of the interferon (IFN)-beta gene. Here, we show that TBK1 is activated by autophosphorylation at residue Ser172. Structures of TBK1 bound to two inhibitors showed that TBK1 has the IkappaB kinase fold with three distinct domains: the kinase domain, the ubiquitin-like domain, and the scaffold and dimerization domain. However, the overall structures of the TBK1 monomer and its dimer are different from IKKbeta in the arrangements of the three domains and in dimer formation. Phosphorylation of IRF-3 by TBK1 in vitro results in its oligomerization, and phosphorylation of residue Ser386 plays a key role in IRF-3 activation.
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==Function==
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Structural Insights into the Functions of TBK1 in Innate Antimicrobial Immunity.,Shu C, Sankaran B, Chaton CT, Herr AB, Mishra A, Peng J, Li P Structure. 2013 Jun 5. pii: S0969-2126(13)00155-X. doi:, 10.1016/j.str.2013.04.025. PMID:23746807<ref>PMID:23746807</ref>
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[[http://www.uniprot.org/uniprot/TBK1_MOUSE TBK1_MOUSE]] Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFN-alpha and IFN-beta. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS or SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating IKKA/CHUK or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1 (By similarity).<ref>PMID:10581243</ref> <ref>PMID:15661922</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4jlc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JLC OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023746807</ref><references group="xtra"/><references/>
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*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Li, P.]]
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[[Category: Li, P]]
[[Category: Kinase]]
[[Category: Kinase]]
[[Category: Protein kinase]]
[[Category: Protein kinase]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 15:00, 21 December 2014

Crystal structure of mouse TBK1 bound to SU6668

4jlc, resolution 3.00Å

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