2riq

From Proteopedia

Revision as of 05:48, 27 February 2008

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

Overview

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.

About this Structure

2RIQ is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Known structural/functional Sites: , , , and . Full crystallographic information is available from OCA.

Reference

A Third Zinc-binding Domain of Human Poly(ADP-ribose) Polymerase-1 Coordinates DNA-dependent Enzyme Activation., Langelier MF, Servent KM, Rogers EE, Pascal JM, J Biol Chem. 2008 Feb 15;283(7):4105-14. Epub 2007 Nov 30. PMID:18055453

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