1S8E

Crystal structure of Mre11-3

1S8E の概要

• エントリーDOI: 10.2210/pdb1s8e/pdb
• 分子名称: exonuclease putative, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: dna double-strand break, mre11, rad50, replication
• 由来する生物種: Pyrococcus furiosus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77995.01

構造登録者

Hopfner, K.P. (登録日: 2004-02-02, 公開日: 2004-08-10, 最終更新日: 2024-05-29)

主引用文献

Arthur, L.M.,Gustausson, K.,Hopfner, K.P.,Carson, C.T.,Stracker, T.H.,Karcher, A.,Felton, D.,Weitzman, M.D.,Tainer, J.A.,Carney, J.P.
Structural and functional analysis of Mre11-3
Nucleic Acids Res., 32:1886-1893, 2004

PubMed Abstract: The Mre11, Rad50 and Nbs1 proteins make up the conserved multi-functional Mre11 (MRN) complex involved in multiple, critical DNA metabolic processes including double-strand break repair and telomere maintenance. The Mre11 protein is a nuclease with broad substrate recognition, but MRN-dependent processes requiring the nuclease activity are not clearly defined. Here, we report the functional and structural characterization of a nuclease-deficient Mre11 protein termed mre11-3. Importantly, the hmre11-3 protein has wild-type ability to bind DNA, Rad50 and Nbs1; however, nuclease activity was completely abrogated. When expressed in cell lines from patients with ataxia telangiectasia-like disorder (ATLD), hmre11-3 restored the formation of ionizing radiation-induced foci. Consistent with the biochemical results, the 2.3 A crystal structure of mre11-3 from Pyrococcus furiosus revealed an active site structure with a wild-type-like metal-binding environment. The structural analysis of the H85L mutation provides a detailed molecular basis for the ability of mre11-3 to bind but not hydrolyze DNA. Together, these results establish that the mre11-3 protein provides an excellent system for dissecting nuclease-dependent and independent functions of the Mre11 complex.

PubMed: 15047855
DOI: 10.1093/nar/gkh343

実験手法

X-RAY DIFFRACTION (2.3 Å)