Local Structural Elements in the Mostly Unstructured Transcriptional Activation Domain of Human p53

DNA transcription is initiated by a small regulatory region of transactivators known as the transactivation domain. In contrast to the rapid progress made on the functional aspect of this promiscuous domain, its structural feature is still poorly characterized. Here, our multidimensional NMR study r...

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Published in:The Journal of biological chemistry 2000-09, Vol.275 (38), p.29426-29432
Main Authors: Lee, Hyun, Mok, K. Hun, Muhandiram, Ranjith, Park, Kyu-Hwan, Suk, Jae-Eun, Kim, Do-Hyung, Chang, Jun, Sung, Young Chul, Choi, Kwan Yong, Han, Kyou-Hoon
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Humans
Molecular Sequence Data
Sequence Analysis, Protein
Transcription, Genetic
Transcriptional Activation
Tumor Suppressor Protein p53 - chemistry
Tumor Suppressor Protein p53 - genetics
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Summary:DNA transcription is initiated by a small regulatory region of transactivators known as the transactivation domain. In contrast to the rapid progress made on the functional aspect of this promiscuous domain, its structural feature is still poorly characterized. Here, our multidimensional NMR study reveals that an unbound full-length p53 transactivation domain, although similar to the recently discovered group of loosely folded proteins in that it does not have tertiary structure, is nevertheless populated by an amphipathic helix and two nascent turns. The helix is formed by residues Thr18–Leu26(Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu), whereas the two turns are formed by residues Met40–Met44 and Asp48–Trp53, respectively. It is remarkable that these local secondary structures are selectively formed by functionally critical and positionally conserved hydrophobic residues present in several acidic transactivation domains. This observation suggests that such local structures are general features of acidic transactivation domains and may represent “specificity determinants” (Ptashne, M., and Gann, A. A. F. (1997),Nature 386, 569–577) that are important for transcriptional activity.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M003107200