Structural origin for the transcriptional activity of human p53

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Structural origin for the transcriptional activity of human p53
Si Hyung Lee; Kyu Hwan Park; Do Hyung Kim; Dong Ho Choung; Jae Eun Suk; Do Hyung Kim; Jun Chang; Young Chul Sung; Kwan Yong Choi; Kyou Hoon Han
Bibliographic Citation
BMB Reports, vol. 34, no. 1, pp. 73-79
Publication Year
Transcriptional activation domains are known to be inherently "unstructured" with no tertiary structure. A recent NMR study, however, has shown that the transactivation domain in human p53 is populated with an amphipathic helix and two nascent turns. This suggests that the presence of such local secondary structures within the overall "unstructured" structural framework is a general feature of acidic transactivation domains. These pre-existing local structures in p53, formed selectively by positionally conserved hydrophobic residues that are known to be critical for transcriptional activity, thus appear to constitute the specific structural motifs that regulate recognition of the p53 transactivation domain by target proteins. Here, we report the results of a NMR structural comparison between the native human p53 transactivation domain and an inactive mutant (22L,23W→22R,23S). Results show that the mutant has an identical overall structural topology as the native protein, to the extent that the amphipathic helix formed by the residues 18T-26L within the native p53 transactivating domain is preserved in the double mutant. Therefore, the lack of transcriptional activity in the double mutant should be ascribed to the disruption of the essential hydrophobic contacts between the p53 transactivation domain and target proteins due to the (22L,23W→22R,23S) mutation.
mouse double minute 2nuclear magnetic resonancep53transcriptional activation domainUnstructured
Korea Soc-Assoc-Inst
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Division of Bio Technology Innovation > Core Research Facility & Analysis Center > 1. Journal Articles
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