5TUU

Crystal structure of the E2F4-DP1 coiled coil and marked-box domains

5TUU の概要

• エントリーDOI: 10.2210/pdb5tuu/pdb
• 関連するPDBエントリー: 5TUV
• 分子名称: Transcription factor DP1, Transcription factor E2F4, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: transcription factor, cell-cycle regulation, coiled coil domian, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30364.56

構造登録者

Liban, T.J.,Rubin, S.M.,Tripathi, S.M. (登録日: 2016-11-07, 公開日: 2017-05-03, 最終更新日: 2023-10-04)

主引用文献

Liban, T.J.,Medina, E.M.,Tripathi, S.,Sengupta, S.,Henry, R.W.,Buchler, N.E.,Rubin, S.M.
Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family.
Proc. Natl. Acad. Sci. U.S.A., 114:4942-4947, 2017

PubMed Abstract: The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs. We find that although CTD-CM binding is conserved across protein families, Rb and p107 CTDs show clear preferences for different E2Fs. A crystal structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the molecular basis for pocket protein-E2F binding specificity and how cyclin-dependent kinases differentially regulate pocket proteins through CTD phosphorylation. Our structural and biochemical data together with phylogenetic analyses of Rb and E2F proteins support the conclusion that Rb evolved specific structural motifs that confer its unique capacity to bind with high affinity those E2Fs that are the most potent activators of the cell cycle.

PubMed: 28439018
DOI: 10.1073/pnas.1619170114

実験手法

X-RAY DIFFRACTION (2.251 Å)