2N9E

Structure of SUMO-2 bound to phosphorylated RAP80 SIM

2N9E の概要

• エントリーDOI: 10.2210/pdb2n9e/pdb
• NMR情報: BMRB: 25901
• 分子名称: BRCA1-A complex subunit RAP80, Small ubiquitin-related modifier 2 (2 entities in total)
• 機能のキーワード: sumo-2-phosphorap80, sumo-2-phosphosim, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : Q96RL1 P61956
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12466.63

構造登録者

Anamika, A.,Spyracopoulos, L. (登録日: 2015-11-15, 公開日: 2016-01-20, 最終更新日: 2024-11-20)

主引用文献

Anamika,Spyracopoulos, L.
Molecular Basis for Phosphorylation-dependent SUMO Recognition by the DNA Repair Protein RAP80.
J.Biol.Chem., 291:4417-4428, 2016

PubMed Abstract: Recognition and repair of double-stranded DNA breaks (DSB) involves the targeted recruitment of BRCA tumor suppressors to damage foci through binding of both ubiquitin (Ub) and the Ub-like modifier SUMO. RAP80 is a component of the BRCA1 A complex, and plays a key role in the recruitment process through the binding of Lys(63)-linked poly-Ub chains by tandem Ub interacting motifs (UIM). RAP80 also contains a SUMO interacting motif (SIM) just upstream of the tandem UIMs that has been shown to specifically bind the SUMO-2 isoform. The RAP80 tandem UIMs and SIM function collectively for optimal recruitment of BRCA1 to DSBs, although the molecular basis of this process is not well understood. Using NMR spectroscopy, we demonstrate that the RAP80 SIM binds SUMO-2, and that both specificity and affinity are enhanced through phosphorylation of the canonical CK2 site within the SIM. The affinity increase results from an enhancement of electrostatic interactions between the phosphoserines of RAP80 and the SIM recognition module within SUMO-2. The NMR structure of the SUMO-2·phospho-RAP80 complex reveals that the molecular basis for SUMO-2 specificity is due to isoform-specific sequence differences in electrostatic SIM recognition modules.

PubMed: 26719330
DOI: 10.1074/jbc.M115.705061

実験手法

SOLUTION NMR