1s8e
From Proteopedia
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Crystal structure of Mre11-3
Overview
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.
About this Structure
1S8E is a Single protein structure of sequence from Pyrococcus furiosus with MN as ligand. Full crystallographic information is available from OCA.
Reference
Structural and functional analysis of Mre11-3., Arthur LM, Gustausson K, Hopfner KP, Carson CT, Stracker TH, Karcher A, Felton D, Weitzman MD, Tainer J, Carney JP, Nucleic Acids Res. 2004 Mar 26;32(6):1886-93. Print 2004. PMID:15047855
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