1s8e

From Proteopedia

Crystal structure of Mre11-3

Structural highlights

1s8e is a 2 chain structure with sequence from Pyrococcus furiosus DSM 3638. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MRE11_PYRFU Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Arthur LM, Gustausson K, Hopfner KP, Carson CT, Stracker TH, Karcher A, Felton D, Weitzman MD, Tainer J, Carney JP. Structural and functional analysis of Mre11-3. Nucleic Acids Res. 2004 Mar 26;32(6):1886-93. Print 2004. PMID:15047855 doi:10.1093/nar/gkh343