TBX5: Difference between revisions

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{{STRUCTURE_2x6v| PDB=2x6v | SIZE=400| SCENE= |right|CAPTION=TBX5 complex with DNA, PEG and Mg+2 ion, [[2x6v]] }}

{{STRUCTURE_2x6v| PDB=2x6v | SIZE=400| SCENE= |right|CAPTION=TBX5 dimer complex with DNA, PEG and Mg+2 ion, [[2x6v]] }}

=Introduction=

TBX5 is a protein of which mutants can cause the Holt-Oram syndrome. It has been crystallised twice, one with and one without the corresponding DNA. It is different from the [[TBX3]] and [[Brachyury]] structures in the way that it dimerises, and that it has been bound to a half-site rather than a full palindromic site. The difference in dimerisations calls into question whether these proteins dimerise naturally or, as their in vivo predicted binding sites suggest, bind monomerically to the DNA. These proteins generally do not dimerise in conserved regions.

'''TBX5''' is a protein of which mutants can cause the Holt-Oram syndrome. It has been crystallised twice, one with and one without the corresponding DNA. It is different from the [[TBX3]] and [[Brachyury]] structures in the way that it dimerises, and that it has been bound to a half-site rather than a full palindromic site. The difference in dimerisations calls into question whether these proteins dimerise naturally or, as their in vivo predicted binding sites suggest, bind monomerically to the DNA. These proteins generally do not dimerise in conserved regions.

A bioinformatic search suggests that two nuclear localisation signals exist, one in the T-box domain and one in the transactivation domain.

A bioinformatic search suggests that two nuclear localisation signals exist, one in the T-box domain and one in the transactivation domain. See also [[Transcription and RNA Processing]].

=Crystal structure=

Lone TBX5 crystallised in the P212121 space group to 1.9 Å resolution, whereas that with the half-site DNA crystallised to 2.2 Å resolution in the P6122 space group. TBX5 has a very similar structure to those solved structures of TBX3 and Brachyury, and superimposing TBX3 and TBX5 give a root mean standard deviation of 2.1 Å over 174 atoms. These structures will be discussed in turn.

Lone TBX5 crystallised in the P212121 space group to 1.9 Å resolution ([[2x6u]]), whereas that with the half-site DNA crystallised to 2.2 Å resolution in the P6122 space group ([[2x6v]]). TBX5 has a very similar structure to those solved structures of TBX3 and Brachyury, and superimposing TBX3 and TBX5 give a root mean standard deviation of 2.1 Å over 174 atoms. These structures will be discussed in turn.

==TBX5 bound to DNA ([[2x6v]])==

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Lone TBX5 crystallised with just one TBX5 in the asymmetric unit, failing to form the disulphide bridge as seen in the first crystal structure. However, the region which formed the minor contacts with the other TBX5 in the DNA-bound crystal structure is disordered in this structure, as predicted by the RONN algorithm. Similar disordered predictions are seen in Brachyury, although in the DNA-bound state this has a well-defined electron density (this could be stabilised by the crystal packing, however) and is part of a long loop region. The 310C helix is also disordered in the apo-form of TBX5.

==Additional Resources==

=3D structures of TBX5=

[[T-box proteins]]

=Additional Resources=

For additional information, see: [[Transcription and RNA Processing]]

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@@ Line 1: / Line 1: @@
-{{STRUCTURE_2x6v|  PDB=2x6v  | SIZE=400| SCENE= |right|CAPTION=TBX5 complex with DNA, PEG and Mg+2 ion, [[2x6v]] }}
+{{STRUCTURE_2x6v|  PDB=2x6v  | SIZE=400| SCENE= |right|CAPTION=TBX5 dimer complex with DNA, PEG and Mg+2 ion, [[2x6v]] }}
 =Introduction=
-TBX5 is a protein of which mutants can cause the Holt-Oram syndrome.  It has been crystallised twice, one with and one without the corresponding DNA.  It is different from the [[TBX3]] and [[Brachyury]] structures in the way that it dimerises, and that it has been bound to a half-site rather than a full palindromic site.  The difference in dimerisations calls into question whether these proteins dimerise naturally or, as their <i>in vivo</i> predicted binding sites suggest, bind monomerically to the DNA.  These proteins generally do not dimerise in conserved regions.
+'''TBX5''' is a protein of which mutants can cause the Holt-Oram syndrome.  It has been crystallised twice, one with and one without the corresponding DNA.  It is different from the [[TBX3]] and [[Brachyury]] structures in the way that it dimerises, and that it has been bound to a half-site rather than a full palindromic site.  The difference in dimerisations calls into question whether these proteins dimerise naturally or, as their <i>in vivo</i> predicted binding sites suggest, bind monomerically to the DNA.  These proteins generally do not dimerise in conserved regions.
-A bioinformatic search suggests that two nuclear localisation signals exist, one in the T-box domain and one in the transactivation domain.
+A bioinformatic search suggests that two nuclear localisation signals exist, one in the T-box domain and one in the transactivation domain.  See also [[Transcription and RNA Processing]].
 =Crystal structure=
-Lone TBX5 crystallised in the P2<sub>1</sub>2<sub>1</sub>2<sub>1</sub> space group to 1.9 Å resolution, whereas that with the half-site DNA crystallised to 2.2 Å resolution in the P6<sub>1</sub>22 space group.  TBX5 has a very similar structure to those solved structures of TBX3 and Brachyury, and superimposing TBX3 and TBX5 give a root mean standard deviation of 2.1 Å over 174 atoms.  These structures will be discussed in turn.
+Lone TBX5 crystallised in the P2<sub>1</sub>2<sub>1</sub>2<sub>1</sub> space group to 1.9 Å resolution ([[2x6u]]), whereas that with the half-site DNA crystallised to 2.2 Å resolution in the P6<sub>1</sub>22 space group ([[2x6v]]).  TBX5 has a very similar structure to those solved structures of TBX3 and Brachyury, and superimposing TBX3 and TBX5 give a root mean standard deviation of 2.1 Å over 174 atoms.  These structures will be discussed in turn.
 ==TBX5 bound to DNA ([[2x6v]])==
@@ Line 23: / Line 23: @@
 Lone TBX5 crystallised with just one TBX5 in the asymmetric unit, failing to form the disulphide bridge as seen in the first crystal structure.  However, the region which formed the minor contacts with the other TBX5 in the DNA-bound crystal structure is disordered in this structure, as predicted by the RONN algorithm.  Similar disordered predictions are seen in Brachyury, although in the DNA-bound state this has a well-defined electron density (this could be stabilised by the crystal packing, however) and is part of a long loop region.  The 3<sub>10</sub>C helix is also disordered in the apo-form of TBX5.
-==Additional Resources==
+=3D structures of TBX5=
+[[T-box proteins]]
+=Additional Resources=
 For additional information, see: [[Transcription and RNA Processing]]
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