4FBW

Crystal structure of an unfused Mre11-Nbs1 complex with two manganese ions per active site

Summary for 4FBW

• Entry DOI: 10.2210/pdb4fbw/pdb
• Related: 4FCX 4fbk 4fbq
• Descriptor: DNA repair protein rad32, DNA repair and telomere maintenance protein nbs1, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: dna double-strand break repair, nuclease, hydrolase, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Schizosaccharomyces pombe (Fission yeast); More
• Cellular location: Nucleus : Q09683 O43070
• Total number of polymer chains: 4
• Total formula weight: 108937.83

Authors

Schiller, C.B.,Lammens, K.,Hopfner, K.P. (deposition date: 2012-05-23, release date: 2012-06-20, Last modification date: 2024-02-28)

Primary citation

Schiller, C.B.,Lammens, K.,Guerini, I.,Coordes, B.,Feldmann, H.,Schlauderer, F.,Mockel, C.,Schele, A.,Strasser, K.,Jackson, S.P.,Hopfner, K.P.
Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling.
Nat.Struct.Mol.Biol., 19:693-700, 2012

PubMed Abstract: The Mre11-Rad50-Nbs1 (MRN) complex tethers, processes and signals DNA double-strand breaks, promoting genomic stability. To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1. Two Nbs1 subunits stretch around the outside of the nuclease domains of Mre11, with one subunit additionally bridging and locking the Mre11 dimer via a highly conserved asymmetrical binding motif. Our results show that Mre11 forms a flexible dimer and suggest that Nbs1 not only is a checkpoint adaptor but also functionally influences Mre11-Rad50. Clinical mutations in Mre11 are located along the Nbs1-interaction sites and weaken the Mre11-Nbs1 interaction. However, they differentially affect DNA repair and telomere maintenance in Saccharomyces cerevisiae, potentially providing insight into their different human disease pathologies.

PubMed: 22705791
DOI: 10.1038/nsmb.2323

Experimental method

X-RAY DIFFRACTION (2.2 Å)