3THO

Crystal structure of Mre11:Rad50 in its ATP/ADP bound state

3THO の概要

• エントリーDOI: 10.2210/pdb3tho/pdb
• 関連するPDBエントリー: 3THN
• 分子名称: Probable DNA double-strand break repair Rad50 ATPase, Exonuclease, putative, ADENOSINE-5'-DIPHOSPHATE, ... (8 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Thermotoga maritima; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88571.29

構造登録者

Moeckel, C.,Lammens, K. (登録日: 2011-08-19, 公開日: 2011-10-12, 最終更新日: 2024-11-27)

主引用文献

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

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: 21937514
DOI: 10.1093/nar/gkr749

実験手法

X-RAY DIFFRACTION (2.6081 Å)