1O9K

Crystal structure of the retinoblastoma tumour suppressor protein bound to E2F peptide

1O9K の概要

• エントリーDOI: 10.2210/pdb1o9k/pdb
• 関連するPDBエントリー: 1AD6 1GH6 1GUX 1H24 1H25 1N4M 1PJM 2AZE
• 分子名称: RETINOBLASTOMA-ASSOCIATED PROTEIN, TRANSCRIPTION FACTOR E2F1, ... (4 entities in total)
• 機能のキーワード: apoptosis, tumour suppressor, cell cycle regulation, dna-binding
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus: P06400 P06400 Q01094
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 181974.62

構造登録者

Xiao, B.,Spencer, J.,Clements, A.,Ali-Khan, N.,Mittnacht, S.,Broceno, C.,Burghammer, M.,Perrakis, A.,Marmorstein, R.,Gamblin, S.J. (登録日: 2002-12-16, 公開日: 2003-03-06, 最終更新日: 2024-10-23)

主引用文献

Xiao, B.,Spencer, J.,Clements, A.,Ali-Khan, N.,Mittnacht, S.,Broceno, C.,Burghammer, M.,Perrakis, A.,Marmorstein, R.,Gamblin, S.J.
Crystal Structure of the Retinoblastoma Tumor Suppressor Protein Bound to E2F and the Molecular Basis of its Regulation
Proc.Natl.Acad.Sci.USA, 100:2363-, 2003

PubMed Abstract: The retinoblastoma tumor suppressor protein (pRb) regulates the cell cycle, facilitates differentiation, and restrains apoptosis. Furthermore, dysfunctional pRb is thought to be involved in the development of most human malignancies. Many of the functions of pRb are mediated by its regulation of the E2F transcription factors. To understand the structural basis for this regulation, we have determined the crystal structure of a fragment of E2F in complex with the pocket domain of the tumor suppressor protein. The pRb pocket, comprising the A and B cyclin-like domains, is the major focus of tumourigenic mutations in the protein. The fragment of E2F used in our structural studies, residues 409-426 of E2F-1, represents the core of the pRb-binding region of the transcription factor. The structure shows that E2F binds at the interface of the A and B domains of the pocket making extensive interactions with conserved residues from both. We show by solution studies that a second site, probably contained within the "marked box" region of E2F, is responsible for additional interactions with the pRb pocket but is insufficient for complex formation on its own. In addition, we show that the interaction of the core binding fragment of E2F with pRb is inhibited by phosphorylation of the tumor suppressor protein by CDK2cyclin DE. Finally, our data reveal that the tight binding of the human papillomavirus E7 oncoprotein to pRb prevents subsequent interactions with the marked box region of E2F but not with its core binding region.

PubMed: 12598654
DOI: 10.1073/PNAS.0436813100

実験手法

X-RAY DIFFRACTION (2.6 Å)