2L31

Human PARP-1 zinc finger 2

2L31 の概要

• エントリーDOI: 10.2210/pdb2l31/pdb
• 関連するPDBエントリー: 2L30
• NMR情報: BMRB: 17158
• 分子名称: Poly [ADP-ribose] polymerase 1, ZINC ION (2 entities in total)
• 機能のキーワード: zinc finger, transferase, dna repair protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12659.86

構造登録者

Neuhaus, D.,Eustermann, S.,Yang, J.,Videler, H. (登録日: 2010-08-30, 公開日: 2011-02-02, 最終更新日: 2024-05-01)

主引用文献

Eustermann, S.,Videler, H.,Yang, J.C.,Cole, P.T.,Gruszka, D.,Veprintsev, D.,Neuhaus, D.
The DNA-binding domain of human PARP-1 interacts with DNA single-strand breaks as a monomer through its second zinc finger.
J.Mol.Biol., 407:149-170, 2011

PubMed Abstract: Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly abundant chromatin-associated enzyme present in all higher eukaryotic cell nuclei, where it plays key roles in the maintenance of genomic integrity, chromatin remodeling and transcriptional control. It binds to DNA single- and double-strand breaks through an N-terminal region containing two zinc fingers, F1 and F2, following which its C-terminal catalytic domain becomes activated via an unknown mechanism, causing formation and addition of polyadenosine-ribose (PAR) to acceptor proteins including PARP-1 itself. Here, we report a biophysical and structural characterization of the F1 and F2 fingers of human PARP-1, both as independent fragments and in the context of the 24-kDa DNA-binding domain (F1+F2). We show that the fingers are structurally independent in the absence of DNA and share a highly similar structural fold and dynamics. The F1+F2 fragment recognizes DNA single-strand breaks as a monomer and in a single orientation. Using a combination of NMR spectroscopy and other biophysical techniques, we show that recognition is primarily achieved by F2, which binds the DNA in an essentially identical manner whether present in isolation or in the two-finger fragment. F2 interacts much more strongly with nicked or gapped DNA ligands than does F1, and we present a mutational study that suggests origins of this difference. Our data suggest that different DNA lesions are recognized by the DNA-binding domain of PARP-1 in a highly similar conformation, helping to rationalize how the full-length protein participates in multiple steps of DNA single-strand breakage and base excision repair.

PubMed: 21262234
DOI: 10.1016/j.jmb.2011.01.034

実験手法

SOLUTION NMR