Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer.
Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer.
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DOI:
10.1016/j.str.2009.11.011
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发表时间:
2010-02-10
期刊:
影响因子:
--
通讯作者:
Chen L
中科院分区:
文献类型:
--
作者:
Chen Y;Dey R;Chen L
Recent studies suggest that p53 binds predominantly to consensus sites composed of two decameric half-sites with zero spacing in vivo. Here we report the crystal structure of the p53 core domain bound to a full consensus site as a tetramer at 2.13Å resolution. Comparison with previously reported structures of p53 dimer:DNA complexes and a chemically trapped p53 tetramer:DNA complex reveals that DNA binding by the p53 core domain is a cooperative self-assembling process accompanied by structural changes of the p53 dimer and DNA. Each p53 monomer interacts with its two neighboring subunits through two different protein-protein interfaces. The DNA is largely B-form and shows no discernible bend, but the central base-pairs between the two half sites display a significant slide. The extensive protein-protein and protein-DNA interactions explain the high cooperativity and kinetic stability of p53 binding to contiguous decameric sites and the conservation of such binding-site configuration in vivo.
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