Sandbox Reserved 827: Difference between revisions
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Several residues of TBK1 can be modified, by phosphorylation or polyubiquitination. | Several residues of TBK1 can be modified, by phosphorylation or polyubiquitination. | ||
Ser172 belongs to the kinase domain and can be phosphorylated by TBK1 itself, or by another serine kinase. This phosphorylation modifies the conformation of the kinase activation loop (residues L164-G199), making the binding of the substrate possible. When S172 is not phosphorylated, the HPD motif can dock itself between two αhelix of the kinase domain of another promoter. Furthermore, an αhelix 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 DFG domain. This liberates the active site of the other protomer, which can now bind a substrate. | Ser172 belongs to the kinase domain and can be phosphorylated by TBK1 itself, or by another serine kinase. This phosphorylation modifies the conformation of the kinase activation loop (residues L164-G199), making the binding of the substrate possible. When S172 is not phosphorylated, the HPD motif can dock itself between two αhelix of the kinase domain of another promoter. Furthermore, an αhelix 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 DFG domain. This liberates the active site of the other protomer, which can now bind a substrate. | ||
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. | 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. | ||
Revision as of 18:13, 30 December 2013
| This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543. |
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TBK1 stands for Tank Binding Kinase 1. This enzyme is a cytoplasmic serine-threonine kinase, coded by EC=2.7.11.1. It catalyzes the transfer of a phosphate group from an ATP onto a protein, in order to form a phosphoprotein and an ADP. Its primary sequence is 729 residues long. This homodimere is involved in several signalization pathways such as the inhibition of apoptosis, inflammatory response. Its substrates are NF-κ-B, various IRFs (interferon regulatory factors), DDX3X. It is involved in several complexes depending on the cell type and the stimuli.
Possible residue modificationsPossible residue modifications
Several residues of TBK1 can be modified, by phosphorylation or polyubiquitination. Ser172 belongs to the kinase domain and can be phosphorylated by TBK1 itself, or by another serine kinase. This phosphorylation modifies the conformation of the kinase activation loop (residues L164-G199), making the binding of the substrate possible. When S172 is not phosphorylated, the HPD motif can dock itself between two αhelix of the kinase domain of another promoter. Furthermore, an αhelix 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 DFG domain. This liberates the active site of the other protomer, which can now bind a substrate. 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.