2geq: Difference between revisions
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'''Protein-DNA complex'''<br /> | '''Protein-DNA complex'''<br /> | ||
==Overview== | ==Overview== | ||
The p53 tumor suppressor protein binds to DNA as a dimer of dimers to | The p53 tumor suppressor protein binds to DNA as a dimer of dimers to regulate transcription of genes that mediate responses to cellular stress. We have prepared a cross-linked trapped p53 core domain dimer bound to decamer DNA and have determined its structure by x-ray crystallography to 2.3A resolution. The p53 core domain subunits bind nearly symmetrically to opposite faces of the DNA in a head-to-head fashion with a loophelix motif making sequence-specific DNA contacts and bending the DNA by about 20 degrees at the site of protein dimerization. Protein subunit interactions occur over the central DNA minor groove and involve residues from a zinc-binding region. Analysis of tumor derived p53 mutations reveals that the dimerization interface represents a third hot spot for mutation that also includes residues associated with DNA contact and protein stability. Residues associated with p53 dimer formation on DNA are poorly conserved in the p63 and p73 paralogs, possibly contributing to their functional differences. We have used the dimeric protein-DNA complex to model a dimer of p53 dimers bound to icosamer DNA that is consistent with solution bending data and suggests that p53 core domain dimer-dimer contacts are less frequently mutated in human cancer than intra-dimer contacts. | ||
==About this Structure== | ==About this Structure== | ||
2GEQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN and TRS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2GEQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GEQ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Fitzgerald, M | [[Category: Fitzgerald, M X.]] | ||
[[Category: Ho, W | [[Category: Ho, W C.]] | ||
[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
[[Category: TRS]] | [[Category: TRS]] | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:56 2008'' | ||
Revision as of 18:30, 21 February 2008
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Protein-DNA complex
OverviewOverview
The p53 tumor suppressor protein binds to DNA as a dimer of dimers to regulate transcription of genes that mediate responses to cellular stress. We have prepared a cross-linked trapped p53 core domain dimer bound to decamer DNA and have determined its structure by x-ray crystallography to 2.3A resolution. The p53 core domain subunits bind nearly symmetrically to opposite faces of the DNA in a head-to-head fashion with a loophelix motif making sequence-specific DNA contacts and bending the DNA by about 20 degrees at the site of protein dimerization. Protein subunit interactions occur over the central DNA minor groove and involve residues from a zinc-binding region. Analysis of tumor derived p53 mutations reveals that the dimerization interface represents a third hot spot for mutation that also includes residues associated with DNA contact and protein stability. Residues associated with p53 dimer formation on DNA are poorly conserved in the p63 and p73 paralogs, possibly contributing to their functional differences. We have used the dimeric protein-DNA complex to model a dimer of p53 dimers bound to icosamer DNA that is consistent with solution bending data and suggests that p53 core domain dimer-dimer contacts are less frequently mutated in human cancer than intra-dimer contacts.
About this StructureAbout this Structure
2GEQ is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the p53 core domain dimer bound to DNA., Ho WC, Fitzgerald MX, Marmorstein R, J Biol Chem. 2006 Jul 21;281(29):20494-502. Epub 2006 May 22. PMID:16717092
Page seeded by OCA on Thu Feb 21 17:30:56 2008