2RIQ

Crystal Structure of the Third Zinc-binding domain of human PARP-1

Summary for 2RIQ

• Entry DOI: 10.2210/pdb2riq/pdb
• Descriptor: Poly [ADP-ribose] polymerase 1, ZINC ION, ETHANOL, ... (5 entities in total)
• Functional Keywords: zn-binding domain, zn ribbon, zn finger, adp-ribosylation, dna damage, dna repair, dna-binding, glycosyltransferase, metal-binding, nad, nucleus, phosphorylation, transferase, zinc-finger
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P09874
• Total number of polymer chains: 1
• Total formula weight: 18781.06

Authors

Pascal, J.M.,Langelier, M.F.,Servent, K.M. (deposition date: 2007-10-12, release date: 2008-01-08, Last modification date: 2024-02-21)

Primary citation

Langelier, M.F.,Servent, K.M.,Rogers, E.E.,Pascal, J.M.
A Third Zinc-binding Domain of Human Poly(ADP-ribose) Polymerase-1 Coordinates DNA-dependent Enzyme Activation.
J.Biol.Chem., 283:4105-4114, 2008

PubMed Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme with multiple cellular functions, including DNA repair, transcriptional regulation, and cell signaling. PARP-1 has a modular architecture with six independent domains comprising the 113-kDa polypeptide. Two zinc finger domains at the N terminus of PARP-1 bind to DNA and thereby activate the catalytic domain situated at the C terminus of the enzyme. The tight coupling of DNA binding and catalytic activities is critical to the cellular regulation of PARP-1 function; however, the mechanism for coordinating these activities remains an unsolved problem. Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. Biochemical mutagenesis and deletion analysis indicate that this region mediates interdomain contacts important for DNA-dependent enzyme activation. The crystal structure of the third zinc-binding domain reveals a zinc ribbon fold and suggests conserved residues that could form interdomain contacts. The new zinc-binding domain self-associates in the crystal lattice to form a homodimer with a head-totail arrangement. The structure of the homodimer provides a scaffold for assembling the activated state of PARP-1 and suggests a mechanism for coupling the DNA binding and catalytic functions of PARP-1.

PubMed: 18055453
DOI: 10.1074/jbc.M708558200

Experimental method

X-RAY DIFFRACTION (1.7 Å)