5D5K

Crystal Structure NLS from human PARP-2 complexed with Importin alpha delta IBB

5D5K の概要

• エントリーDOI: 10.2210/pdb5d5k/pdb
• 分子名称: Importin subunit alpha-1, Poly [ADP-ribose] polymerase 2 (3 entities in total)
• 機能のキーワード: parp-2 nls, parp-2, poly(adp-ribose)polymerase-2, importin alpha, proton transport
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61234.44

構造登録者

Riccio, A.A.,Cingolani, G.,Pascal, J.M. (登録日: 2015-08-10, 公開日: 2016-06-22, 最終更新日: 2023-09-27)

主引用文献

Riccio, A.A.,Cingolani, G.,Pascal, J.M.
PARP-2 domain requirements for DNA damage-dependent activation and localization to sites of DNA damage.
Nucleic Acids Res., 44:1691-1702, 2016

PubMed Abstract: Poly(ADP-ribose) polymerase-2 (PARP-2) is one of three human PARP enzymes that are potently activated during the cellular DNA damage response (DDR). DDR-PARPs detect DNA strand breaks, leading to a dramatic increase in their catalytic production of the posttranslational modification poly(ADP-ribose) (PAR) to facilitate repair. There are limited biochemical and structural insights into the functional domains of PARP-2, which has restricted our understanding of how PARP-2 is specialized toward specific repair pathways. PARP-2 has a modular architecture composed of a C-terminal catalytic domain (CAT), a central Trp-Gly-Arg (WGR) domain and an N-terminal region (NTR). Although the NTR is generally considered the key DNA-binding domain of PARP-2, we report here that all three domains of PARP-2 collectively contribute to interaction with DNA damage. Biophysical, structural and biochemical analyses indicate that the NTR is natively disordered, and is only required for activation on specific types of DNA damage. Interestingly, the NTR is not essential for PARP-2 localization to sites of DNA damage. Rather, the WGR and CAT domains function together to recruit PARP-2 to sites of DNA breaks. Our study differentiates the functions of PARP-2 domains from those of PARP-1, the other major DDR-PARP, and highlights the specialization of the multi-domain architectures of DDR-PARPs.

PubMed: 26704974
DOI: 10.1093/nar/gkv1376

実験手法

X-RAY DIFFRACTION (1.9 Å)