4YOZ

p107 pocket domain in complex with HPV E7 peptide

4YOZ の概要

• エントリーDOI: 10.2210/pdb4yoz/pdb
• 関連するPDBエントリー: 1GUX 4YOO 4YOS
• 分子名称: Retinoblastoma-like protein 1,Retinoblastoma-like protein 1, HPV E7 peptide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: pocket protein, cyclin box, transcriptional regulator, cell cycle, 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: 44810.47

構造登録者

Liban, T.J.,Guiley, K.Z.,Felthousen, J.G.,Ramanan, P.,Litovchick, L.,Rubin, S.M. (登録日: 2015-03-12, 公開日: 2015-06-24, 最終更新日: 2024-02-28)

主引用文献

Guiley, K.Z.,Liban, T.J.,Felthousen, J.G.,Ramanan, P.,Litovchick, L.,Rubin, S.M.
Structural mechanisms of DREAM complex assembly and regulation.
Genes Dev., 29:961-974, 2015

PubMed Abstract: The DREAM complex represses cell cycle genes during quiescence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130. Upon cell cycle entry, MuvB dissociates from p107/p130 and recruits B-Myb and FoxM1 for up-regulating mitotic gene expression. To understand the biochemical mechanisms underpinning DREAM function and regulation, we investigated the structural basis for DREAM assembly. We identified a sequence in the MuvB component LIN52 that binds directly to the pocket domains of p107 and p130 when phosphorylated on the DYRK1A kinase site S28. A crystal structure of the LIN52-p107 complex reveals that LIN52 uses a suboptimal LxSxExL sequence together with the phosphate at nearby S28 to bind the LxCxE cleft of the pocket domain with high affinity. The structure explains the specificity for p107/p130 over Rb in the DREAM complex and how the complex is disrupted by viral oncoproteins. Based on insights from the structure, we addressed how DREAM is disassembled upon cell cycle entry. We found that p130 and B-Myb can both bind the core MuvB complex simultaneously but that cyclin-dependent kinase phosphorylation of p130 weakens its association. Together, our data inform a novel target interface for studying MuvB and p130 function and the design of inhibitors that prevent tumor escape in quiescence.

PubMed: 25917549
DOI: 10.1101/gad.257568.114

実験手法

X-RAY DIFFRACTION (2.245 Å)