6M3H
Crystal structure of mouse HPF1
Summary for 6M3H
| Entry DOI | 10.2210/pdb6m3h/pdb |
| Descriptor | Histone PARylation factor 1 (2 entities in total) |
| Functional Keywords | cofactor, adp-ribosylation, dna damage response, nuclear protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 39352.25 |
| Authors | |
| Primary citation | 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 Cited by 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: 33589610DOI: 10.1038/s41467-021-21302-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.71 Å) |
Structure validation
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