2PK2

Cyclin box structure of the P-TEFb subunit Cyclin T1 derived from a fusion complex with EIAV Tat

2PK2 の概要

• エントリーDOI: 10.2210/pdb2pk2/pdb
• 関連するPDBエントリー: 1PKW
• 分子名称: Cyclin-T1, Protein Tat (2 entities in total)
• 機能のキーワード: cyclin t1, tat, tar, twinning, transcription regulation p-tefb, cell cycle
• 由来する生物種: Homo sapiens (human,); 詳細
• 細胞内の位置: Host nucleus, host nucleolus : P32544
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161366.55

構造登録者

Anand, K.,Schulte, A.,Fujinaga, K.,Scheffzek, K.,Geyer, M. (登録日: 2007-04-17, 公開日: 2007-07-03, 最終更新日: 2024-02-21)

主引用文献

Anand, K.,Schulte, A.,Fujinaga, K.,Scheffzek, K.,Geyer, M.
Cyclin Box Structure of the P-TEFb Subunit Cyclin T1 Derived from a Fusion Complex with EIAV Tat.
J.Mol.Biol., 370:826-836, 2007

PubMed Abstract: The positive transcription elongation factor b (P-TEFb) is an essential regulator of viral gene expression during the life cycle of human immunodeficiency virus type 1 (HIV-1). Its cyclin T1 subunit forms a ternary complex with the viral transcriptional transactivator (Tat) protein and the transactivation response (TAR) RNA element thereby activating cyclin dependent kinase 9 (Cdk9), which stimulates transcription at the level of chain elongation. We report the structure of the cyclin box domain of human cyclin T1 at a resolution of 2.67 A. The structure was obtained by crystallographic analysis of a fusion protein composed of cyclin T1 linked to the transactivator protein Tat from equine infectious anemia virus (EIAV), which is functionally and structurally related to HIV-1 Tat. The conserved cyclin box domain of cyclin T1 exhibits structural features for interaction with physiological binding partners such as Cdk9. A recognition site for Cdk/Cyclin substrates is partly covered by a cyclin T-specific insert, suggesting specific interactions with regulatory factors. The previously identified Tat/TAR recognition motif (TRM) forms a C-terminal helix that is partly occluded in the cyclin box repeat interface, while cysteine 261 is accessible to form an intermolecular zinc finger with Tat. Residues of the TRM contribute to a positively charged groove that may directly attract RNA molecules. The EIAV Tat protein instead appeared undefined from the electron density map suggesting that it is highly disordered. Functional experiments confirmed the TAR binding properties of the fusion protein and suggested residues on the second cyclin box repeat to contribute to Tat stimulated transcription.

PubMed: 17540406
DOI: 10.1016/j.jmb.2007.04.077

実験手法

X-RAY DIFFRACTION (2.67 Å)