P53-DNA Recognition: Difference between revisions
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<StructureSection load=' | {{BAMBED | ||
|DATE=July 26, 2012 | |||
|OLDID=1472467 | |||
|BAMBEDDOI=10.1002/bmb.20650 | |||
}} | |||
<StructureSection load='' size='400' side='right' ' oldscene='Sandbox_Reserved_170/Complex/6' scene='P53-DNA_Recognition/P53_complex/1' caption='Human p53 core complex with DNA (PDB code [[3kz8]]).'> | |||
''This is a joint project of students at La Cañada High School, La Cañada Flintridge, California USA, and students at the University of Southern California, Los Angeles, California USA, mentored by [[User:Remo Rohs|Professor Remo Rohs]].'' | ''This is a joint project of students at La Cañada High School, La Cañada Flintridge, California USA, and students at the University of Southern California, Los Angeles, California USA, mentored by [[User:Remo Rohs|Professor Remo Rohs]].'' | ||
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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 (<scene oldname='Sandbox_Reserved_170/Complex/6' name='P53-DNA_Recognition/P53_complex/1'>Figure 4: Crystal structure of p53 DBD tetramer-DNA complex</scene>, [[3kz8|PDB ID 3KZ8]]). | 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 (<scene oldname='Sandbox_Reserved_170/Complex/6' name='P53-DNA_Recognition/P53_complex/1'>Figure 4: Crystal structure of p53 DBD tetramer-DNA complex</scene>, [[3kz8|PDB ID 3KZ8]]). | ||
The DBD in tetrameric form binds to a <font color="#e06000">'''DNA response element'''</font> | The DBD in tetrameric form binds to a <font color="#e06000">'''DNA response element'''</font>, 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. | ||
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==Tetramerization Domain== | ==Tetramerization Domain== | ||
Aside from the DBD, the only other domain for which structural information is available is the ''tetramerization domain'' [<scene name='Sandbox_Reserved_170/Tetra/2'>Figure 7: Crystal structure of p53 tetramerization domain</scene>, ([[1c26|PDB ID 1C26]])], 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 (<scene oldname='Sandbox_Reserved_170/Complex/6' name='P53-DNA_Recognition/P53_complex/1'>Figure 4: Crystal structure of p53 DBD tetramer-DNA complex</scene>). | |||
Aside from the DBD, the only other domain for which structural information is available is the ''tetramerization domain'' [ | |||
=Further Reading= | =Further Reading= | ||
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A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69. [http://www.ncbi.nlm.nih.gov/pubmed/20334529 PMID:20334529].</ref>.<br/> | A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69. [http://www.ncbi.nlm.nih.gov/pubmed/20334529 PMID:20334529].</ref>.<br/> | ||
</StructureSection> | </StructureSection> | ||
=3D structures of p53= | |||
[[P53]] | |||
=Acknowledgements= | =Acknowledgements= | ||
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=References= | =References= | ||
<references/> | <references/> | ||
[[Category:Featured in BAMBED]] | |||