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A conformational switch regulates p53 DNA binding

Emamzadah, Soheila
Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4590 - 2013/08/29
Abstract The p53 tumour suppressor gene encodes for a transcription factor that encompasses a sequence-specific DNA-binding and an oligomerization domains. This gene is the most frequently mutated gene in human cancers. It remains unclear how p53 recognizes its DNA target sites on the genome. We describe here the structures of p53 in absence and in complex with DNA. Structure and kinetic analyses of p53-DNA complexes reveal that p53 recognizes its specific DNA target sites via an induced fit mechanism. The affinities of p53 for specific and non-specific DNA are similar, but the off-rates are much different. The loop L1 of the DNA-binding domain of p53 undergoes a conformational switch. Overall, these results reveal the importance of the conformational switch of loop L1 in the DNA binding properties of p53. We also describe here the first structure of p53 in complex with the natural CDKN1A (p21) p53-response element.
Keywords P53AffinityCrystallographieOff-rate
URN: urn:nbn:ch:unige-303166
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Research group Groupe Halazonetis
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EMAMZADAH, Soheila. A conformational switch regulates p53 DNA binding. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:30316

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Deposited on : 2013-10-09

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