6M3H

Crystal structure of mouse HPF1

6M3H の概要

• エントリーDOI: 10.2210/pdb6m3h/pdb
• 分子名称: Histone PARylation factor 1 (2 entities in total)
• 機能のキーワード: cofactor, adp-ribosylation, dna damage response, nuclear protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39352.25

構造登録者

Sun, F.H.,Yun, C.H. (登録日: 2020-03-03, 公開日: 2021-03-03, 最終更新日: 2023-11-29)

主引用文献

Sun, F.H.,Zhao, P.,Zhang, N.,Kong, L.L.,Wong, C.C.L.,Yun, C.H.
HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones.
Nat Commun, 12:1028-1028, 2021

PubMed Abstract: Upon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors to initiate DNA repair. Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. Here, we report the crystal structures of human HPF1/PARP1-CAT ΔHD complex at 1.98 Å resolution, and mouse and human HPF1 at 1.71 Å and 1.57 Å resolution, respectively. Our structures and mutagenesis data confirm that the structural insights obtained in a recent HPF1/PARP2 study by Suskiewicz et al. apply to PARP1. Moreover, we quantitatively characterize the key residues necessary for HPF1/PARP1 binding. Our data show that through salt-bridging to Glu284/Asp286, Arg239 positions Glu284 to catalyze serine ADP-ribosylation, maintains the local conformation of HPF1 to limit PARP1 automodification, and facilitates HPF1/PARP1 binding by neutralizing the negative charge of Glu284. These findings, along with the high-resolution structural data, may facilitate drug discovery targeting PARP1.

PubMed: 33589610
DOI: 10.1038/s41467-021-21302-4

実験手法

X-RAY DIFFRACTION (1.71 Å)