Sandbox Reserved 827: Difference between revisions
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The DFG (Asp-Phe-Gly) motif and Ser172 are involved in the regulation of the kinase activity. | The DFG (Asp-Phe-Gly) motif and Ser172 are involved in the regulation of the kinase activity. | ||
'''Ubiquitin-like domain :''' (<scene name='56/568025/Uld/2'> | '''Ubiquitin-like domain :''' (<scene name='56/568025/Uld/2'>ULD</scene>) from amino acid 309 to amino acid 385: it contains five β strands which form a hydrophobic interface, giving the protein a high structural homology with ubiquitin. | ||
The '''<scene name='56/568025/Lz/1'>leucine zipper</scene> ''' (between amino acid 408 and amino acid 651) and the '''<scene name='56/568025/Coiledcoil/1'>coiled coil domain</scene>''' (between amino acid 626 and amino acid 713) are responsible for the dimerization of the protomer. Together they form the '''scaffolding dimerization domain''' (SDD). This domain presents many alpha-helix. | The '''<scene name='56/568025/Lz/1'>leucine zipper</scene> ''' (between amino acid 408 and amino acid 651) and the '''<scene name='56/568025/Coiledcoil/1'>coiled coil domain</scene>''' (between amino acid 626 and amino acid 713) are responsible for the dimerization of the protomer. Together they form the '''scaffolding dimerization domain''' (SDD). This domain presents many alpha-helix. | ||
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'''<scene name='56/568025/Atp/1'>ATP binding domain</scene>:''' from amino acid 15 to amino acid 23. This is where is bound the ATP needed for the reaction catalyzed by TBK1. This domain is really close to the catalytic residue in the 3D shape of the enzyme. | '''<scene name='56/568025/Atp/1'>ATP binding domain</scene>:''' from amino acid 15 to amino acid 23. This is where is bound the ATP needed for the reaction catalyzed by TBK1. This domain is really close to the catalytic residue in the 3D shape of the enzyme. | ||
The KD and the | The KD and the ULD interact with each other: the ULD with the C-lobe of the KD. There is a <scene name='56/568025/Kd-ubl_interactions/2'>hydrogen bound</scene> between Tyr325 in the ULD and Glu109 in the KD. Moreover <scene name='56/568025/Kd-ubl_interactions/1'>Lys323</scene> in the ULD makes favourable electrostatic interactions with Glu109-KD. | ||
==Dimer== | ==Dimer== | ||
ULD and KD also contribute to dimerization thanks to several interactions with the SDD of the opposite subunit in the homodimer. | |||
There are several hydrogen bonds between the KD (N- and C-lobes) and the SDD of the opposite subunit: a salt bridge is formed between Asp33 in the N-lobe and Lys589 in the SDD and the strands the β7-β8 in the C-love interact with the SDD. A | There are several hydrogen bonds between the KD (N- and C-lobes) and the SDD of the opposite subunit: a | ||
<scene name='56/568025/33-589/2'>salt bridge</scene> is formed between Asp33 in the N-lobe and Lys589 in the SDD and the strands the β7-β8 in the C-love interact with the SDD. A “ | |||
<scene name='56/568025/Egr-seq/1'>EGR</scene>” sequence (residues 355–357) in the ULD interacts with the SDD: Glu355-ULD interacts with Arg444-SDD (salt bridge) and Trp445-SDD (hydrogen bonds). | |||
=Possible residue modifications= | =Possible residue modifications= | ||
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== Inflammatory response == | == Inflammatory response == | ||
The inflammatory response begin with the formation of the complex TBK1-TANK-TRAF. That allows phosphorylation of IRF3, IRF7 and DDX3X. Then these phosphorylated proteins form homodimers and they are translocated into the nucleus, where they activate transcription of interferon regulatory factors (IFN). | The inflammatory response begin with the formation of the complex TBK1-TANK-TRAF. That allows phosphorylation of IRF3, IRF7 and DDX3X. Then these phosphorylated proteins form homodimers and they are translocated into the nucleus, where they activate transcription of interferon regulatory factors (IFN). Interferons are proteins synthetized in response to recognition of pathogen. They can interact with viral replication and inhibit it. | ||
== Anti-apoptosis == | == Anti-apoptosis == | ||
The complex TBK1-TANK-TRAF phosphorylates an inhibitor of NFkappaB, which finally activates NFkappaB, an anti-apoptotic transcription factor. | The complex TBK1-TANK-TRAF phosphorylates an inhibitor of NFkappaB, which inactivates it. This finally activates NFkappaB, an anti-apoptotic transcription factor. | ||
= Diseases = | = Diseases = | ||