3THO
Crystal structure of Mre11:Rad50 in its ATP/ADP bound state
Summary for 3THO
| Entry DOI | 10.2210/pdb3tho/pdb |
| Related | 3THN |
| Descriptor | Probable DNA double-strand break repair Rad50 ATPase, Exonuclease, putative, ADENOSINE-5'-DIPHOSPHATE, ... (8 entities in total) |
| Functional Keywords | adenosine triphosphate, bacterial proteins, dna breaks, double-stranded, dna repair, dna repair enzymes, dna-binding proteins, endodeoxyribonucleases, exodeoxyribonucleases, models, molecular, scattering, small angle, thermotoga maritima, abc atpase, nuclease, hydrolase, hydrolase-dna binding protein complex, hydrolase/dna binding protein |
| Biological source | Thermotoga maritima More |
| Total number of polymer chains | 2 |
| Total formula weight | 88571.29 |
| Authors | Moeckel, C.,Lammens, K. (deposition date: 2011-08-19, release date: 2011-10-12, Last modification date: 2024-11-27) |
| Primary citation | Mockel, C.,Lammens, K.,Schele, A.,Hopfner, K.P. ATP driven structural changes of the bacterial Mre11:Rad50 catalytic head complex. Nucleic Acids Res., 40:914-927, 2012 Cited by PubMed Abstract: DNA double-strand breaks (DSBs) threaten genome stability in all kingdoms of life and are linked to cancerogenic chromosome aberrations in humans. The Mre11:Rad50 (MR) complex is an evolutionarily conserved complex of two Rad50 ATPases and a dimer of the Mre11 nuclease that senses and processes DSBs and tethers DNA for repair. ATP binding and hydrolysis by Rad50 is functionally coupled to DNA-binding and tethering, but also regulates Mre11's nuclease in processing DNA ends. To understand how ATP controls the interaction between Mre11 and Rad50, we determined the crystal structure of Thermotoga maritima (Tm) MR trapped in an ATP/ADP state. ATP binding to Rad50 induces a large structural change from an open form with accessible Mre11 nuclease sites into a closed form. Remarkably, the NBD dimer binds in the Mre11 DNA-binding cleft blocking Mre11's dsDNA-binding sites. An accompanying large swivel of the Rad50 coiled coil domains appears to prepare the coiled coils for DNA tethering. DNA-binding studies show that within the complex, Rad50 likely forms a dsDNA-binding site in response to ATP, while the Mre11 nuclease module retains a ssDNA-binding site. Our results suggest a possible mechanism for ATP-dependent DNA tethering and DSB processing by MR. PubMed: 21937514DOI: 10.1093/nar/gkr749 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6081 Å) |
Structure validation
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