Proteopedia - User contributions [en]

Sandbox Reserved 1647

2021-01-14T18:32:58Z

Justine Marc:

<Structure load='5t1j' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
==Introduction==
TBX21 or T-bet is a [https://en.wikipedia.org/wiki/Transcription_factor transcription factor], more precisely a [[T-box proteins]]. The DNA binding domain of T-bet has a dimer structure composes of two identical chains (<scene name='86/868180/Chain_a_bis/1'>A</scene> / <scene name='86/868180/Chain_b/1'>B</scene> ) with a total molecular weight of 76,37 kDA. This binding domain allows it to bind itself to the DNA on promotor or regulator area. The particularity of this T-box protein is that is able to link two DNA molecules with only one dimer. Moreover, it is able to link two areas of the same DNA molecules which are far from each other and thus create a chromatin loop.
The main function of this transcription factor is to direct [https://en.wikipedia.org/wiki/T_helper_cell TH1 cells differentiation] from naive CD4+ cells. Nevertheless, the action field of T-bet is larger than classical T-box protein.

== Structure and structural interactions ==
===Primary Structure===

[[Image:T-Bet primary structure.PNG|thumb |left|upright=3 |schema of primary structure of T-bet protein from ''Mus musculus'']]
The DNA binding domain of T-bet from ''Mus musculus'' for a monomer is located between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene>.

=== Secondary structure and interactions ===

The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of β-strands and α-helices 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.

== Some roles of TBX21 ==
=== Regulation of Th cells differentiation by TBX21 ===
The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet.
We know that T-bet initiates Th1 lineage development from naive Thp cells by activating Th1 genetics and repressing the opposing Th2 programs. Th1 cells stimulate cellular immune response while Th2 stimulates humoral immune response and induces antibody production.

[[Image:TBET.jpg]]

Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the formation of the super elongation complex (SEC). Th1 genes are occupied by RNA polymerase II in Thp cells, while T-bet-mediated recruitment of P-TEFb and mediator and activates transcriptional elongation giving place to an increased differentiation of Thp into Th1.

T-bet can also regulates Th1 cell differentiation by directly initiating gamma interferon (IFN-γ) transcription and by suppressing Th2-specific transcription factor GATA-3. The T-bet induced expression of IFN-γ derives Th precursor cells to differentiate into Th1 effector cells.
This stimulation of IFN-γ can takes place thanks to the action of a nuclear tyrosine kinase, c-Abl. C-Abl induces phosphorylation of T-bet at tyrosine residues <scene name='86/868180/Tyr219/1'>TYR 219</scene>, <scene name='86/868180/Tyr265/1'>TYR 265</scene>, and <scene name='86/868180/Tyr304/1'>TYR 304</scene>. C-Abl phosphorylates the tyrosine residues within the T-box domain, which is the DNA-binding domain of T-bet. This phosphorylation leads to conformational changes of the T-box domain to facilitate the DNA-binding activity of T-bet and appears to play a crucial role in the IFN-γ promoter-binding activity of T-bet.

Recently, many studies have reported that T-bet also modulates other Th cell lineages, including Th17, Treg, and follicular Th (TFH) cells, in coordination with many transcription factors, such as the retinoic acid-related orphan receptor-𝛾t (ROR𝛾t), runt-related transcription factor 3 (RUNX3), and B-cell lymphoma-6 (BCL6).These findings suggest that T-bet is a transcription factor that is critical for fine-tuning Th cell development.

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-14T18:32:22Z

Justine Marc:

<Structure load='5t1j' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
==Introduction==
TBX21 or T-bet is a [https://en.wikipedia.org/wiki/Transcription_factor transcription factor], more precisely a [[T-box proteins]]. The DNA binding domain of T-bet has a dimer structure composes of two identical chains (<scene name='86/868180/Chain_a_bis/1'>A</scene> / <scene name='86/868180/Chain_b/1'>B</scene> ) with a total molecular weight of 76,37 kDA. This binding domain allows it to bind itself to the DNA on promotor or regulator area. The particularity of this T-box protein is that is able to link two DNA molecules with only one dimer. Moreover, it is able to link two areas of the same DNA molecules which are far from each other and thus create a chromatin loop.
The main function of this transcription factor is to direct [https://en.wikipedia.org/wiki/T_helper_cell TH1 cells differentiation] from naive CD4+ cells. Nevertheless, the action field of T-bet is larger than classical T-box protein.

== Structure and structural interactions ==
===Primary Structure===

[[Image:T-Bet primary structure.PNG|thumb |left|upright=3 |schema of primary structure of T-bet protein from ''Mus musculus'']]
The DNA binding domain of T-bet from ''Mus musculus'' for a monomer is located between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene>.

=== Secondary structure and interactions ===

The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of β-strands and α-helices 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.

== Some roles of TBX21 ==
=== Regulation of Th cells differentiation by TBX21 ===
The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet.
We know that T-bet initiates Th1 lineage development from naive Thp cells by activating Th1 genetics and repressing the opposing Th2 programs. Th1 cells stimulate cellular immune response while Th2 stimulates humoral immune response and induces antibody production.

[[Image:TBET.jpg]]

Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the formation of the super elongation complex (SEC). Th1 genes are occupied by RNA polymerase II in Thp cells, while T-bet-mediated recruitment of P-TEFb and mediator and activates transcriptional elongation giving place to an increased differentiation of Thp into Th1.

T-bet can also regulates Th1 cell differentiation by directly initiating gamma interferon (IFN-γ) transcription and by suppressing Th2-specific transcription factor GATA-3. The T-bet induced expression of IFN-γ derives Th precursor cells to differentiate into Th1 effector cells.
This stimulation of IFN-γ can takes place thanks to the action of a nuclear tyrosine kinase, c-Abl. C-Abl induces phosphorylation of T-bet at tyrosine residues <scene name='86/868180/Tyr219/1'>TYR 219</scene>, <scene name='86/868180/Tyr265/1'>TYR 265</scene>, and <scene name='86/868180/Tyr304/1'>TYR 304</scene>. C-Abl phosphorylates the tyrosine residues within the T-box domain, which is the DNA-binding domain of T-bet. This phosphorylation leads to conformational changes of the T-box domain to facilitate the DNA-binding activity of T-bet and appears to play a crucial role in the IFN-γ promoter-binding activity of T-bet.

Recently, many studies have reported that T-bet also modulates other Th cell lineages, including Th17, Treg, and follicular Th (TFH) cells, in coordination with many transcription factors, such as the retinoic acid-related orphan receptor-𝛾t (ROR𝛾t), runt-related transcription factor 3 (RUNX3), and B-cell lymphoma-6 (BCL6).These findings suggest that T-bet is a transcription factor that is critical for fine-tuning Th cell development.

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-14T18:22:17Z

Justine Marc:

<Structure load='5t1j' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
==Introduction==
TBX21 or T-bet is a [https://en.wikipedia.org/wiki/Transcription_factor transcription factor], more precisely a [[T-box proteins]]. The DNA binding domain of T-bet has a dimer structure composes of two identical chains (<scene name='86/868180/Chain_a_bis/1'>A</scene> / <scene name='86/868180/Chain_b/1'>B</scene> ) with a total molecular weight of 76,37 kDA. This binding domain allows it to bind itself to the DNA on promotor or regulator area. The particularity of this T-box protein is that is able to link two DNA molecules with only one dimer. Moreover, it is able to link two areas of the same DNA molecules which are far from each other and thus create a chromatin loop.
The main function of this transcription factor is to direct [https://en.wikipedia.org/wiki/T_helper_cell TH1 cells differentiation] from naive CD4+ cells. Nevertheless, the action field of T-bet is larger than classical T-box protein.

== Structure and structural interactions ==
===Primary Structure===

[[Image:T-Bet primary structure.PNG|thumb |left|upright=3 |schema of primary structure of T-bet protein from ''Mus musculus'']]
The DNA binding domain of T-bet from ''Mus musculus'' for a monomer is located between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene>.

=== Secondary structure and interactions ===

The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of β-strands and α-helices 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. 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.

== Some roles of TBX21 ==
=== Regulation of Th cells differentiation by TBX21 ===
The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet.
We know that T-bet initiates Th1 lineage development from naive Thp cells by activating Th1 genetics and repressing the opposing Th2 programs. Th1 cells stimulate cellular immune response while Th2 stimulates humoral immune response and induces antibody production.

[[Image:TBET.jpg]]

Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the formation of the super elongation complex (SEC). Th1 genes are occupied by RNA polymerase II in Thp cells, while T-bet-mediated recruitment of P-TEFb and mediator and activates transcriptional elongation giving place to an increased differentiation of Thp into Th1.

T-bet can also regulates Th1 cell differentiation by directly initiating gamma interferon (IFN-γ) transcription and by suppressing Th2-specific transcription factor GATA-3. The T-bet induced expression of IFN-γ derives Th precursor cells to differentiate into Th1 effector cells.
This stimulation of IFN-γ can takes place thanks to the action of a nuclear tyrosine kinase, c-Abl. C-Abl induces phosphorylation of T-bet at tyrosine residues 219, 265, and 304. C-Abl phosphorylates the tyrosine residues within the T-box domain, which is the DNA-binding domain of T-bet. This phosphorylation leads to conformational changes of the T-box domain to facilitate the DNA-binding activity of T-bet and appears to play a crucial role in the IFN-γ promoter-binding activity of T-bet.

Recently, many studies have reported that T-bet also modulates other Th cell lineages, including Th17, Treg, and follicular Th (TFH) cells, in coordination with many transcription factors, such as the retinoic acid-related orphan receptor-𝛾t (ROR𝛾t), runt-related transcription factor 3 (RUNX3), and B-cell lymphoma-6 (BCL6).These findings suggest that T-bet is a transcription factor that is critical for fine-tuning Th cell development.

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-14T13:27:56Z

Justine Marc:

{{Sandbox_Reserved_ESBS20_}}
<Structure load='5t1j' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
==Introduction==
TBX21 or T-bet is a [https://en.wikipedia.org/wiki/Transcription_factor transcription factor], more precisely a [[T-box proteins]]. T-bet has a dimer structure composes of two identical chains (<scene name='86/868180/Chain_a_bis/1'>A</scene> / <scene name='86/868180/Chain_b/1'>B</scene> ) with a total molecular weight of 76,37 kDA. Its binding domain allows it to bind itself to the DNA on promotor or regulator area. The particularity of this T-box protein is that is able to link two DNA molecules or two areas of the same DNA molecules which are far from each other.

== Structure and structural interactions ==

=== Secondary structure and interactions ===

The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of β-strands and α-helices 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 K313 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 K313 allows TBX21 to bind with the DNA sequence. Secondly, the phosphorylation of some residues allows TBX21 to interact with several proteins : the phosphorylation of T302 allows TBX21 to interact with NFAT, the one of Y304 allows TBX21 to interact with RUNX1, the one of S508 allows the interaction with NF-кB p65 and finally the one of Y525 allows the interaction with GATA-3.

== Some roles of TBX21 ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-13T18:14:14Z

Justine Marc:

{{Sandbox_Reserved_ESBS20_}}
== Structure ==
<StructureSection load='5t1j' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Secondary structure and interactions ==

The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of β-strands and α-helices 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 K313 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 K313 allows TBX21 to bind with the DNA sequence. Secondly, the phosphorylation of some residues allows TBX21 to interact with several proteins : the phosphorylation of T302 allows TBX21 to interact with NFAT, the one of Y304 allows TBX21 to interact with RUNX1, the one of S508 allows the interaction with NF-кB p65 and finally the one of Y525 allows the interaction with GATA-3.

== Functions ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-13T14:32:22Z

Justine Marc:

File:Tbet modifié.pse

2021-01-13T14:18:35Z

Justine Marc:

Sandbox Reserved 1647

2021-01-13T14:02:31Z

Justine Marc:

<Structure load='<Structure load='5t1j' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> {{Sandbox_Reserved_ESBS20_}}
==Structure
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-13T13:48:50Z

Justine Marc:

<Structure load='5t1j.pdb' size='350' frame='true' caption='TBX21' /> {{Sandbox_Reserved_ESBS20_}}
==Your Heading Here (maybe something like 'Structure')== Structure
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-13T13:46:50Z

Justine Marc:

<Structure load='5t1j.pdb' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />{{Sandbox_Reserved_ESBS20_}}
==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1647

2021-01-13T13:36:35Z

Justine Marc:

<Structure load='5t1j' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />{{Sandbox_Reserved_ESBS20_}}
==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>