title: Local structural elements in the mostly unstructured transcriptional activation domain of human p53.
abstract: 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 Thr(18)-Leu(26) (Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu), whereas the two turns are formed by residues Met(40)-Met(44) and Asp(48)-Trp(53), 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.
authors.affiliation: Protein Engineering Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong, P. O. Box 115, Taejon 305-600, South Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Mok
authors.forename: R
authors.initials: R
authors.lastname: Muhandiram
authors.forename: K H
authors.initials: KH
authors.lastname: Park
authors.forename: J E
authors.initials: JE
authors.lastname: Suk
authors.forename: D H
authors.initials: DH
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: Y C
authors.initials: YC
authors.lastname: Sung
authors.forename: K Y
authors.initials: KY
authors.lastname: Choi
authors.forename: K H
authors.initials: KH
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53