4CRI

Crystal Structure of 53BP1 tandem tudor domains in complex with methylated K810 Rb peptide

4CRI の概要

• エントリーDOI: 10.2210/pdb4cri/pdb
• 分子名称: TUMOR SUPPRESSOR P53-BINDING PROTEIN 1, RB1 PROTEIN (3 entities in total)
• 機能のキーワード: peptide binding protein, tumour suppressor prb, 53bp1
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus: Q12888
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 42778.12

構造登録者

Krojer, T.,Johansson, C.,Gileadi, C.,Fedorov, O.,Carr, S.,La Thangue, N.B.,Vollmar, M.,Crawley, L.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.,Oppermann, U. (登録日: 2014-02-26, 公開日: 2014-08-06, 最終更新日: 2023-12-20)

主引用文献

Carr, S.M.,Munro, S.,Zalmas, L.,Fedorov, O.,Johansson, C.,Krojer, T.,Sagum, C.A.,Bedford, M.T.,Oppermann, U.,La Thangue, N.B.
Lysine Methylation-Dependent Binding of 53BP1 to the Prb Tumor Suppressor.
Proc.Natl.Acad.Sci.USA, 111:11341-, 2014

PubMed Abstract: The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle progression and mediator of the DNA damage response. Lysine methylation at K810, which occurs within a critical Cdk phosphorylation motif, holds pRb in the hypophosphorylated growth-suppressing state. We show here that methyl K810 is read by the tandem tudor domain containing tumor protein p53 binding protein 1 (53BP1). Structural elucidation of 53BP1 in complex with a methylated K810 pRb peptide emphasized the role of the 53BP1 tandem tudor domain in recognition of the methylated lysine and surrounding residues. Significantly, binding of 53BP1 to methyl K810 occurs on E2 promoter binding factor target genes and allows pRb activity to be effectively integrated with the DNA damage response. Our results widen the repertoire of cellular targets for 53BP1 and suggest a previously unidentified role for 53BP1 in regulating pRb tumor suppressor activity.

PubMed: 25049398
DOI: 10.1073/PNAS.1403737111

実験手法

X-RAY DIFFRACTION (2.35 Å)