Sandbox Reserved 827: Difference between revisions
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'''Phosphorylation :''' <scene name='56/568025/Ser172/2'>Ser172</scene> belongs to the kinase domain and can be phosphorylated by TBK1 itself, or by another serine kinase. This phosphorylation modifies the conformation of the <scene name='56/568025/Activation_loop/1'>kinase activation loop</scene> (residues L164-G199), making the binding of the substrate possible. When S172 is not phosphorylated, the <scene name='56/568025/Hpd/1'>HPD motif</scene> can dock itself between two αhelix of the kinase domain of another promoter. Furthermore, an <scene name='56/568025/Helix/1'>helix</scene> containing the residues between D167 and L173 occupies the active site of this other protomer. Therefore, the active domain is not available for the binding of the substrate. But when S172 is phosphorylated, it can bind itself on the kinase domain of its own protomer, as the HPD domain which docks in the kinase domain in an intramolecular way, coming closer to the <scene name='56/568025/Dfg/1'>DFG</scene> domain. This liberates the active site of the other protomer, which can now bind a substrate. <ref name="transact">PMID:22619329</ref> | '''Phosphorylation :''' <scene name='56/568025/Ser172/2'>Ser172</scene> belongs to the kinase domain and can be phosphorylated by TBK1 itself, or by another serine kinase. This phosphorylation modifies the conformation of the <scene name='56/568025/Activation_loop/1'>kinase activation loop</scene> (residues L164-G199), making the binding of the substrate possible. When S172 is not phosphorylated, the <scene name='56/568025/Hpd/1'>HPD motif</scene> can dock itself between two αhelix of the kinase domain of another promoter. Furthermore, an <scene name='56/568025/Helix/1'>helix</scene> containing the residues between D167 and L173 occupies the active site of this other protomer. Therefore, the active domain is not available for the binding of the substrate. But when S172 is phosphorylated, it can bind itself on the kinase domain of its own protomer, as the HPD domain which docks in the kinase domain in an intramolecular way, coming closer to the <scene name='56/568025/Dfg/1'>DFG</scene> domain. This liberates the active site of the other protomer, which can now bind a substrate. <ref name="transact">PMID:22619329</ref> | ||
[[Image:Dimere.jpg|400px|left|thumb| When S172 isn't phosphorylated, the activation loop binds to the active site of another protomer, providing the phosphorylation of substrates. <ref name="transact" />]] | [[Image:Dimere.jpg|400px|left|thumb| When S172 isn't phosphorylated, the activation loop binds to the active site of another protomer, providing the phosphorylation of substrates. <ref name="transact" />]] | ||
[[Image:Activationloop2.jpg|400px|center|thumb| When S172 is phosphorylated, the activation loop comes closer to the KD, thanks to the docking of HPD. One protomer is in blue, the other in orange. <ref name="transact" />]] | [[Image:Activationloop2.jpg|400px|center|thumb| When S172 is phosphorylated, the activation loop comes closer to the KD, thanks to the docking of HPD. One protomer is in blue, the other in orange. <ref name="transact" />]] | ||
[[Image:transactivation.jpg|400px|left|thumb| Hypothecal diagram of the transactivation mechanism of TBK1. <ref name="transact" />]] | |||
The autophosphorylation between two subunit of a dimer is not really probable, since when the protein is dimeric, the two kinase domains are located at the opposite of one another. Therefore, the phosphorylation of Ser172 is done either by the concerned protomer, either by the kinase domain of another TBK1 dimer when TBK1 are involved in scaffolding complexes. <ref name="transact" /> | The autophosphorylation between two subunit of a dimer is not really probable, since when the protein is dimeric, the two kinase domains are located at the opposite of one another. Therefore, the phosphorylation of Ser172 is done either by the concerned protomer, either by the kinase domain of another TBK1 dimer when TBK1 are involved in scaffolding complexes. <ref name="transact" /> | ||
S172 can also be phosphorylated by kinases such as IKKB (also known as IKBKB), and dephosphorylated by phosphatases such as PPM1B. | S172 can also be phosphorylated by kinases such as IKKB (also known as IKBKB), and dephosphorylated by phosphatases such as PPM1B. | ||
