4iwq

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{{STRUCTURE_4iwq| PDB=4iwq | SCENE= }}
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==Crystal structure and mechanism of activation of TBK1==
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===Crystal structure and mechanism of activation of TBK1===
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<StructureSection load='4iwq' size='340' side='right' caption='[[4iwq]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23453971}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4iwq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IWQ 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=1FV:N-{3-[(5-CYCLOPROPYL-2-{[3-(MORPHOLIN-4-YLMETHYL)PHENYL]AMINO}PYRIMIDIN-4-YL)AMINO]PROPYL}CYCLOBUTANECARBOXAMIDE'>1FV</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4iw0|4iw0]], [[4iwp|4iwp]], [[4iwo|4iwo]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAK, TBK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4iwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iwq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iwq RCSB], [http://www.ebi.ac.uk/pdbsum/4iwq 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 I (TBK1) plays a key role in the innate immune system by integrating signals from pattern-recognition receptors. Here, we report the X-ray crystal structures of inhibitor-bound inactive and active TBK1 determined to 2.6 A and 4.0 A resolution, respectively. The structures reveal a compact dimer made up of trimodular subunits containing an N-terminal kinase domain (KD), a ubiquitin-like domain (ULD), and an alpha-helical scaffold dimerization domain (SDD). Activation rearranges the KD into an active conformation while maintaining the overall dimer conformation. Low-resolution SAXS studies reveal that the missing C-terminal domain (CTD) extends away from the main body of the kinase dimer. Mutants that interfere with TBK1 dimerization show significantly reduced trans-autophosphorylation but retain the ability to bind adaptor proteins through the CTD. Our results provide detailed insights into the architecture of TBK1 and the molecular mechanism of activation.
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==Function==
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Crystal structure and mechanism of activation of TANK-binding kinase 1.,Larabi A, Devos JM, Ng SL, Nanao MH, Round A, Maniatis T, Panne D Cell Rep. 2013 Mar 28;3(3):734-46. doi: 10.1016/j.celrep.2013.01.034. Epub 2013, Feb 28. PMID:23453971<ref>PMID:23453971</ref>
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[[http://www.uniprot.org/uniprot/TBK1_HUMAN TBK1_HUMAN]] 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 NF-kappa-B inhibitor alpha/NFKBIA, IKBKB 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. Phosphorylates Borna disease virus (BDV) P protein.<ref>PMID:10581243</ref> <ref>PMID:10783893</ref> <ref>PMID:11839743</ref> <ref>PMID:12692549</ref> <ref>PMID:12702806</ref> <ref>PMID:14703513</ref> <ref>PMID:15485837</ref> <ref>PMID:15489227</ref> <ref>PMID:15367631</ref> <ref>PMID:18583960</ref> <ref>PMID:21270402</ref> <ref>PMID:21464307</ref> <ref>PMID:21617041</ref> <ref>PMID:21138416</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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[[4iwq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IWQ OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023453971</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Larabi, A.]]
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[[Category: Larabi, A]]
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[[Category: Panne, D.]]
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[[Category: Panne, D]]
[[Category: Atp binding]]
[[Category: Atp binding]]
[[Category: Kinase]]
[[Category: Kinase]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 12:33, 21 December 2014

Crystal structure and mechanism of activation of TBK1

4iwq, resolution 3.00Å

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