P53-DNA Recognition: Difference between revisions

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===Domain Architecture and Tetramerization===
===Domain Architecture and Tetramerization===


<Structure load='P53tetra.pdb.zip' size='250' frame='true' align='left' caption='Figure 4: Crystal structure of p53 tetramerization domain, [http://proteopedia.com/wiki/index.php/1c26 PDB ID 1C26].' scene='Sandbox_Reserved_170/Tetra/2' />
The p53 protein consists of the N-terminal transactivation domain, the DNA binding domain ('''DBD''') or core, the tetramerization domain, and the C-terminal regulatory domain ('''Figure 3'''). This Proteopedia page discusses protein-DNA recognition by p53, thus focusing on the DBD of p53 ('''Figure 4''').


The p53 protein consists of the N-terminal transactivation domain, the DNA binding domain ('''DBD''') or core, the tetramerization domain, and the C-terminal regulatory domain ('''Figure 3'''). This Proteopedia page discusses protein-DNA recognition by p53, thus focusing on the DBD of p53 ('''Figure 5'''). (The only other domain for which structural information is available is the ''tetramerization domain'' ['''Figure 4''', <scene name='Sandbox_Reserved_170/Tetra/2'>restore initial scene</scene>], which forms as a dimer of dimers with one alpha helix and one beta strand contributed by each p53 monomer.)
<Structure load='3kz8bio-4mon.pdb.zip' size='400' frame='true' align='right' caption='Figure 4: Crystal structure of p53 DBD tetramer-DNA complex, [http://proteopedia.com/wiki/index.php/3kz8 PDB ID 3KZ8].' oldscene='Sandbox_Reserved_170/Complex/6' scene='P53-DNA_Recognition/P53_complex/1'/>
 
<Structure load='3kz8bio-4mon.pdb.zip' size='400' frame='true' align='right' caption='Figure 5: Crystal structure of p53 DBD tetramer-DNA complex, [http://proteopedia.com/wiki/index.php/3kz8 PDB ID 3KZ8].' oldscene='Sandbox_Reserved_170/Complex/6' scene='P53-DNA_Recognition/P53_complex/1'/>


The DBD in tetrameric form binds to a <font color="#e06000">'''DNA response element'''</font> (<scene oldname='Sandbox_Reserved_170/Complex/6' name='P53-DNA_Recognition/P53_complex/1'>restore initial scene</scene>), which consists of two DNA half sites. These decameric half sites can be separated by a DNA spacer of flexible length but in this case, the spacer is of length zero base pairs. The <scene oldname='Sandbox_Reserved_170/Complex/7' name='P53-DNA_Recognition/P53_complex/2'>p53 tetramer binds DNA as a dimer of dimers</scene> with each <font color='e000e0'>'''magenta'''</font>-<font color='00c0c0'>'''cyan'''</font> dimer binding to one half site of the response element<ref>Kitayner M, Rozenberg H, Kessler N, Rabinovich D, Shaulov L, Haran TE, Shakked Z. Structural basis of DNA recognition by p53 tetramers. Mol Cell. 2006 Jun 23;22(6):741-53. [http://www.ncbi.nlm.nih.gov/pubmed/16793544 PMID:16793544].</ref>.
The DBD in tetrameric form binds to a <font color="#e06000">'''DNA response element'''</font> (<scene oldname='Sandbox_Reserved_170/Complex/6' name='P53-DNA_Recognition/P53_complex/1'>restore initial scene</scene>), which consists of two DNA half sites. These decameric half sites can be separated by a DNA spacer of flexible length but in this case, the spacer is of length zero base pairs. The <scene oldname='Sandbox_Reserved_170/Complex/7' name='P53-DNA_Recognition/P53_complex/2'>p53 tetramer binds DNA as a dimer of dimers</scene> with each <font color='e000e0'>'''magenta'''</font>-<font color='00c0c0'>'''cyan'''</font> dimer binding to one half site of the response element<ref>Kitayner M, Rozenberg H, Kessler N, Rabinovich D, Shaulov L, Haran TE, Shakked Z. Structural basis of DNA recognition by p53 tetramers. Mol Cell. 2006 Jun 23;22(6):741-53. [http://www.ncbi.nlm.nih.gov/pubmed/16793544 PMID:16793544].</ref>.


The p53 DBD assumes the conformation of an <scene name='Sandbox_Reserved_170/Beta/1'>immunoglobulin-like fold consisting of a beta sandwich</scene>, which binds the response element in the major groove. A functionally important <scene name='Sandbox_Reserved_170/Zn/1'>Zn2+ ion coordinates the Cys176, His179, Cys238, Cys242 residues</scene> and, thus, stabilizes the fold of the DBD.
The p53 DBD assumes the conformation of an <scene name='Sandbox_Reserved_170/Beta/1'>immunoglobulin-like fold consisting of a beta sandwich</scene>, which binds the response element in the major groove. A functionally important <scene name='Sandbox_Reserved_170/Zn/1'>Zn2+ ion coordinates the Cys176, His179, Cys238, Cys242 residues</scene> and, thus, stabilizes the fold of the DBD.
<Structure load='P53tetra.pdb.zip' size='250' frame='true' align='left' caption='Figure 5: Crystal structure of p53 tetramerization domain, [http://proteopedia.com/wiki/index.php/1c26 PDB ID 1C26].' scene='Sandbox_Reserved_170/Tetra/2' />
The only other domain for which structural information is available is the ''tetramerization domain'' ['''Figure 5''', <scene name='Sandbox_Reserved_170/Tetra/2'>restore initial scene</scene>], which forms as a dimer of dimers with one alpha helix and one beta strand contributed by each p53 monomer.


===Protein-Protein Interactions===
===Protein-Protein Interactions===