期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 18, 期 4, 页码 423-U54出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2038
关键词
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资金
- National Cancer Institute [CA117638, CA92584, CA77325]
- US National Intitutes of Health [1Z01ES102765-01]
- Department of Energy, Office of Biological and Environmental Research [DE-AC02-05CH11231]
- Lawrence Berkeley National Laboratory
- United States Department of Energy [DE-AC02-05CH11231]
The Rad50 ABC-ATPase complex with Mre11 nuclease is essential for dsDNA break repair, telomere maintenance and ataxia telangiectasia-mutated kinase checkpoint signaling. How Rad50 affects Mre11 functions and how ABC-ATPases communicate nucleotide binding and ligand states across long distances and among protein partners are questions that have remained obscure. Here, structures of Mre11-Rad50 complexes define the Mre11 2-helix Rad50 binding domain (RBD) that forms a four-helix interface with Rad50 coiled coils adjoining the ATPase core. Newly identified effector and basic-switch helix motifs extend the ABC-ATPase signature motif to link ATP-driven Rad50 movements to coiled coils binding Mre11, implying an similar to 30-angstrom pull on the linker to the nuclease domain. Both RBD and basic-switch mutations cause clastogen sensitivity. Our new results characterize flexible ATP-dependent Mre11 regulation, defects in cancer-linked RBD mutations, conserved superfamily basic switches and motifs effecting ATP-driven conformational change, and they provide a unified comprehension of ABC-ATPase activities.
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