7S81

Structure of human PARP1 domains (Zn1, Zn3, WGR, HD) bound to a DNA double strand break.

7S81 の概要

• エントリーDOI: 10.2210/pdb7s81/pdb
• 関連するPDBエントリー: 7S68 7S6H 7S6M
• 分子名称: DNA (5'-D(*AP*TP*GP*CP*GP*GP*CP*CP*GP*CP*AP*T)-3'), Poly [ADP-ribose] polymerase 1, ZINC ION, ... (6 entities in total)
• 機能のキーワード: parp, adp-ribose transferase, dna break detection, zinc finger, dna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 260411.98

構造登録者

Rouleau-Turcotte, E.,Pascal, J.M. (登録日: 2021-09-17, 公開日: 2022-06-29, 最終更新日: 2023-10-18)

主引用文献

Rouleau-Turcotte, E.,Krastev, D.B.,Pettitt, S.J.,Lord, C.J.,Pascal, J.M.
Captured snapshots of PARP1 in the active state reveal the mechanics of PARP1 allostery.
Mol.Cell, 82:2939-2951.e5, 2022

PubMed Abstract: PARP1 rapidly detects DNA strand break damage and allosterically signals break detection to the PARP1 catalytic domain to activate poly(ADP-ribose) production from NAD. PARP1 activation is characterized by dynamic changes in the structure of a regulatory helical domain (HD); yet, there are limited insights into the specific contributions that the HD makes to PARP1 allostery. Here, we have determined crystal structures of PARP1 in isolated active states that display specific HD conformations. These captured snapshots and biochemical analysis illustrate HD contributions to PARP1 multi-domain and high-affinity interaction with DNA damage, provide novel insights into the mechanics of PARP1 allostery, and indicate how HD active conformations correspond to alterations in the catalytic region that reveal the active site to NAD. Our work deepens the understanding of PARP1 catalytic activation, the dynamics of the binding site of PARP inhibitor compounds, and the mechanisms regulating PARP1 retention on DNA damage.

PubMed: 35793673
DOI: 10.1016/j.molcel.2022.06.011

実験手法

X-RAY DIFFRACTION (3.6 Å)