Sandbox Reserved 1647: Difference between revisions
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The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of <scene name='86/868180/Helix_and_strand/1'>β-strands and α-helix</scene> and is involved in both dimerization and DNA binding. The crystal structure of the α-helices of the T-box domain bound to DNA strongly suggests that the amino group of <scene name='86/868180/Lys314/1'>K 313</scene> is associated with the phosphate of a DNA base via hydrogen-bond interaction. | The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of <scene name='86/868180/Helix_and_strand/1'>β-strands and α-helix</scene> and is involved in both dimerization and DNA binding. The crystal structure of the α-helices of the T-box domain bound to DNA strongly suggests that the amino group of <scene name='86/868180/Lys314/1'>K 313</scene> is associated with the phosphate of a DNA base via hydrogen-bond interaction. | ||
Thanks to some post-translational modifications of the protein’s residues, the transcription factor TBX21 can bind with DNA and some proteins. Firstly, the ubiquitination of the residue <scene name='86/868180/Lys314/1'>K 313</scene> allows TBX21 to bind with the DNA sequence. Lys-313 was lately found as a key site required for T-bet to interact with the IFN-γ gene promoter and to assure phosphorylation at Thr-302. Secondly, the phosphorylation of some residues allows TBX21 to interact with several proteins : the phosphorylation of <scene name='86/868180/Thr302/1'>T 302</scene> allows TBX21 to interact with NFAT, the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with RUNX1, the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with NF-кB p65 and finaly the one of Y525 allows the interaction with GATA-3. | Thanks to some post-translational modifications of the protein’s residues, the transcription factor TBX21 can bind with DNA and some proteins. Firstly, the ubiquitination of the residue <scene name='86/868180/Lys314/1'>K 313</scene> allows TBX21 to bind with the DNA sequence. Lys-313 was lately found as a key site required for T-bet to interact with the IFN-γ gene promoter and to assure phosphorylation at Thr-302. Secondly, the phosphorylation of some residues allows TBX21 to interact with several proteins : the phosphorylation of <scene name='86/868180/Thr302/1'>T 302</scene> allows TBX21 to interact with NFAT[[https://proteopedia.org/wiki/index.php/2o93]], the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with RUNX1[[https://proteopedia.org/wiki/index.php/1co1]], the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with NF-кB p65[[https://proteopedia.org/wiki/index.php/2i9t]] and finaly the one of Y525 allows the interaction with GATA-3. | ||
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=== TBX21 as an antiasthmatic regulator === | === TBX21 as an antiasthmatic regulator === | ||
Asthma remains one of the commonest chronic inflammatory diseases and has a major impact on the life of sufferers. It is associated with allergy mediated by IgE antibodies.T-bet was found associated with many immune-mediated diseases such as asthma. | Asthma remains one of the commonest chronic inflammatory diseases and has a major impact on the life of sufferers. It is associated with allergy mediated by IgE antibodies[[https://proteopedia.org/wiki/index.php/2r56]].T-bet was found associated with many immune-mediated diseases such as asthma. | ||
In asthmatic airways, Th2 cells are activated and release several cytokines that regulate IgE production and inflammatory cell recruitment, such as eosinophils. Th2 cells and GATA-3 play an important role in allergic inflammation and asthma, and induce IgE production. The asthmatic patients present high levels of total IgE | In asthmatic airways, Th2 cells are activated and release several cytokines that regulate IgE production and inflammatory cell recruitment, such as eosinophils. Th2 cells and GATA-3 play an important role in allergic inflammation and asthma, and induce IgE production. The asthmatic patients present high levels of total IgE. On the contrary, the T-bet gene expression and Th1 pattern, along with the IFN- γ production, are usually associated with non-allergic asthmatics and healthy subjects. | ||
In T-bet structure, ubiquitination takes place at <scene name='86/868180/Lys313/1'>LYS 313</scene>. It has an impact on the stability of the protein and leads to the degradation of the protein by the proteosome. Some research found the role of deubiquitinases involved in T-bet stability and function. As a deubiquitinase, USP10 belongs to the ubiquitin-specificprotease family of cysteine proteases. Cysteine 424 site on USP10[[https://proteopedia.org/wiki/index.php/2lbc]] is crucial for its hydrolase activity. Results have shown that USP10 could interact with T-bet and stabilize it via interaction between Lysine 313 (K313) of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ. | In T-bet structure, ubiquitination takes place at <scene name='86/868180/Lys313/1'>LYS 313</scene>. It has an impact on the stability of the protein and leads to the degradation of the protein by the proteosome. Some research found the role of deubiquitinases involved in T-bet stability and function. As a deubiquitinase, USP10 belongs to the ubiquitin-specificprotease family of cysteine proteases. Cysteine 424 site on USP10[[https://proteopedia.org/wiki/index.php/2lbc]] is crucial for its hydrolase activity. Results have shown that USP10 could interact with T-bet and stabilize it via interaction between Lysine 313 (K313) of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ. | ||