2XVS

Crystal structure of human TTC5 (Strap) C-terminal OB domain

2XVS の概要

• エントリーDOI: 10.2210/pdb2xvs/pdb
• 分子名称: TETRATRICOPEPTIDE REPEAT PROTEIN 5, IODIDE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: antitumor protein, p53 cofactor, stress-response, p300
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus: Q8N0Z6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18660.26

構造登録者

Adams, J.,Pike, A.C.W.,Maniam, S.,Sharpe, T.D.,Coutts, A.S.,Knapp, S.,La Thangue, B.,Bullock, A.N. (登録日: 2010-10-31, 公開日: 2010-11-17, 最終更新日: 2024-05-08)

主引用文献

Adams, C.J.,Pike, A.C.,Maniam, S.,Sharpe, T.D.,Coutts, A.S.,Knapp, S.,La Thangue, N.B.,Bullock, A.N.
The P53 Cofactor Strap Exhibits an Unexpected Tpr Motif and Oligonucleotide-Binding (Ob)-Fold Structure.
Proc.Natl.Acad.Sci.USA, 109:3778-, 2012

PubMed Abstract: Activation of p53 target genes for tumor suppression depends on the stress-specific regulation of transcriptional coactivator complexes. Strap (stress-responsive activator of p300) is activated upon DNA damage by ataxia telangiectasia mutated (ATM) and Chk2 kinases and is a key regulator of the p53 response. In addition to antagonizing Mdm2, Strap facilitates the recruitment of p53 coactivators, including JMY and p300. Strap is a predicted TPR-repeat protein, but shows only limited sequence identity with any protein of known structure. To address this and to elucidate the molecular mechanism of Strap activity we determined the crystal structure of the full-length protein at 2.05 Å resolution. The structure of Strap reveals an atypical six tetratricopeptide repeat (TPR) protein that also contains an unexpected oligonucleotide/oligosaccharide-binding (OB)-fold domain. This previously unseen domain organization provides an extended superhelical scaffold allowing for protein-protein as well as protein-DNA interaction. We show that both of the TPR and OB-fold domains localize to the chromatin of p53 target genes and exhibit intrinsic regulatory activity necessary for the Strap-dependent p53 response.

PubMed: 22362889
DOI: 10.1073/PNAS.1113731109

実験手法

X-RAY DIFFRACTION (1.8 Å)