4DQY

Structure of Human PARP-1 bound to a DNA double strand break

Summary for 4DQY

• Entry DOI: 10.2210/pdb4dqy/pdb
• Descriptor: Poly [ADP-ribose] polymerase 1, DNA (26-MER), ZINC ION, ... (6 entities in total)
• Functional Keywords: parp, poly(adp-ribose) polymerase, dna binding protein, adp-ribosyl transferase, parp-like zinc finger, poly(adp-ribosyl)ation, dna damage detection, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P09874 P09874 P09874
• Total number of polymer chains: 8
• Total formula weight: 193570.52

Authors

Langelier, M.F.,Pascal, J.M. (deposition date: 2012-02-16, release date: 2012-05-30, Last modification date: 2024-02-28)

Primary citation

Langelier, M.F.,Planck, J.L.,Roy, S.,Pascal, J.M.
Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1.
Science, 336:728-732, 2012

PubMed Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) (ADP, adenosine diphosphate) has a modular domain architecture that couples DNA damage detection to poly(ADP-ribosyl)ation activity through a poorly understood mechanism. Here, we report the crystal structure of a DNA double-strand break in complex with human PARP-1 domains essential for activation (Zn1, Zn3, WGR-CAT). PARP-1 engages DNA as a monomer, and the interaction with DNA damage organizes PARP-1 domains into a collapsed conformation that can explain the strong preference for automodification. The Zn1, Zn3, and WGR domains collectively bind to DNA, forming a network of interdomain contacts that links the DNA damage interface to the catalytic domain (CAT). The DNA damage-induced conformation of PARP-1 results in structural distortions that destabilize the CAT. Our results suggest that an increase in CAT protein dynamics underlies the DNA-dependent activation mechanism of PARP-1.

PubMed: 22582261
DOI: 10.1126/science.1216338

Experimental method

X-RAY DIFFRACTION (3.25 Å)