9MJA

PARP1 ART in complex with HPF1 and EB47

Summary for 9MJA

• Entry DOI: 10.2210/pdb9mja/pdb
• EMDB information: 48285 48313
• Descriptor: Poly [ADP-ribose] polymerase 1, Histone PARylation factor 1, 2-[4-[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]carbonylpiperazin-1-yl]-N-(1-oxidanylidene-2,3-dihydroisoindol-4-yl)ethanamide (3 entities in total)
• Functional Keywords: parp1, zinc-finger domains, nicked dna, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 155553.09

Authors

Sverzhinsky, A.,Pascal, J.M. (deposition date: 2024-12-14, release date: 2026-01-21, Last modification date: 2026-03-04)

Primary citation

Sverzhinsky, A.,Xue, H.,Langelier, M.F.,Muniz Correa, M.V.,Del Mundo, J.,Classen, S.,Hammel, M.,Rothenberg, E.,Pascal, J.M.
PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation.
Nat Commun, 2026

PubMed Abstract: PARP1 detection of DNA strand breaks allosterically leads to PARP1 synthesis of poly(ADP-ribose) modifications that signal DNA damage. HPF1 engages activated PARP1 to control modification site selection. Understanding of the mechanism of DNA break detection and catalytic activation is incomplete, due largely to limited structural information for full-length PARP1. Here, single-particle cryo-EM provides views of the full complement of PARP1 domains engaging a DNA single-strand break in the presence of HPF1 and a fragment of binding partner Timeless. Cryo-EM, single-molecule DNA dynamics, and small-angle X-ray scattering analysis indicate that PARP1 remains dynamic even when the multi-domain structure is organized on a DNA break, with the minimal catalytic region displaying high mobility relative to domains engaging damage. We propose that the organization of PARP1 domains on a DNA break releases a tethered, constitutively active catalytic region to modify molecules in a radius surrounding the DNA break site.

PubMed: 41698892
DOI: 10.1038/s41467-026-69375-3

Experimental method

ELECTRON MICROSCOPY (4.3 Å)