6S6V

Resting state of the E. coli Mre11-Rad50 (SbcCD) head complex bound to ATPgS

Summary for 6S6V

• Entry DOI: 10.2210/pdb6s6v/pdb
• EMDB information: 10107
• Descriptor: Nuclease SbcCD subunit D, Nuclease SbcCD subunit C, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: nuclease, dna repair, abc-type atpase, dna double-strand breaks, dna binding protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 330318.47

Authors

Kaeshammer, L.,Saathoff, J.H.,Gut, F.,Bartho, J.,Alt, A.,Kessler, B.,Lammens, K.,Hopfner, K.P. (deposition date: 2019-07-03, release date: 2019-09-04, Last modification date: 2019-11-20)

Primary citation

Kashammer, L.,Saathoff, J.H.,Lammens, K.,Gut, F.,Bartho, J.,Alt, A.,Kessler, B.,Hopfner, K.P.
Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex.
Mol.Cell, 76:382-, 2019

PubMed Abstract: DNA double-strand breaks (DSBs) threaten genome stability throughout life and are linked to tumorigenesis in humans. To initiate DSB repair by end joining or homologous recombination, the Mre11-nuclease Rad50-ATPase complex detects and processes diverse and obstructed DNA ends, but a structural mechanism is still lacking. Here we report cryo-EM structures of the E. coli Mre11-Rad50 homolog SbcCD in resting and DNA-bound cutting states. In the resting state, Mre11's nuclease is blocked by ATP-Rad50, and the Rad50 coiled coils appear flexible. Upon DNA binding, the two coiled coils zip up into a rod and, together with the Rad50 nucleotide-binding domains, form a clamp around dsDNA. Mre11 moves to the side of Rad50, binds the DNA end, and assembles a DNA cutting channel for the nuclease reactions. The structures reveal how Mre11-Rad50 can detect and process diverse DNA ends and uncover a clamping and gating function for the coiled coils.

PubMed: 31492634
DOI: 10.1016/j.molcel.2019.07.035

Experimental method

ELECTRON MICROSCOPY (3.5 Å)