P53-DNA Recognition: Difference between revisions
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==Introduction and Biological Role of the Tumor Suppressor p53== | ==Introduction and Biological Role of the Tumor Suppressor p53== | ||
[[Image:p53-intro.jpg|thumb|left|300px|Figure 1: Crystal structure of a p53 DBD tetramer-DNA complex; [ | [[Image:p53-intro.jpg|thumb|left|300px|Figure 1: Crystal structure of a p53 DBD tetramer-DNA complex; [[3kz8|PDB ID# 3KZ8]]<ref name='kitayner'>Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol. 2010;17(4):423-9. [http://www.ncbi.nlm.nih.gov/pubmed/20364130 PMID:20364130].</ref>.]] | ||
[[Image:consensus.jpg|thumb|right|250px|Figure 2: p53 consensus site; R= A or G, Y= C or T, and W=A or T.]] | [[Image:consensus.jpg|thumb|right|250px|Figure 2: p53 consensus site; R= A or G, Y= C or T, and W=A or T.]] | ||
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The p53 protein consists of the N-terminal transactivation domain, the DNA binding domain ('''DBD''') or core, the tetramerization domain ([[#Tetramerization Domain|see its structure below]]), 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 ([[#Tetramerization Domain|see its structure below]]), 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'''). | ||
<Structure load='3kz8bio-4mon.pdb.zip' size='400' frame='true' align='right' caption='Figure 4: Crystal structure of p53 DBD tetramer-DNA complex, [ | <Structure load='3kz8bio-4mon.pdb.zip' size='400' frame='true' align='right' caption='Figure 4: Crystal structure of p53 DBD tetramer-DNA complex, [[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>. | ||
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==Tetramerization Domain== | ==Tetramerization Domain== | ||
<Structure load='P53tetra.pdb.zip' size='250' frame='true' align='right' caption='Figure 7: Crystal structure of p53 tetramerization domain, [ | <Structure load='P53tetra.pdb.zip' size='250' frame='true' align='right' caption='Figure 7: Crystal structure of p53 tetramerization domain, [[1c26|PDB ID 1C26]].' scene='Sandbox_Reserved_170/Tetra/2' /> | ||
Aside from the DBD, the only other domain for which structural information is available is the ''tetramerization domain'' ['''Figure 7''', <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. The tetramerization domain is ''not present'' in the crystal structure of the DBD (Figure 4). | Aside from the DBD, the only other domain for which structural information is available is the ''tetramerization domain'' ['''Figure 7''', <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. The tetramerization domain is ''not present'' in the crystal structure of the DBD (Figure 4). | ||