4w9m
From Proteopedia
AMPPNP bound Rad50 in complex with dsDNA
Structural highlights
FunctionRAD50_THEMA Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. Rad50 provides an ATP-dependent control of Mre11 by unwinding and/or repositioning DNA ends into the Mre11 active site (By similarity). Publication Abstract from PubMedThe Mre11-Rad50 nuclease-ATPase is an evolutionarily conserved multifunctional DNA double-strand break (DSB) repair factor. Mre11-Rad50's mechanism in the processing, tethering, and signaling of DSBs is unclear, in part because we lack a structural framework for its interaction with DNA in different functional states. We determined the crystal structure of Thermotoga maritima Rad50(NBD) (nucleotide-binding domain) in complex with Mre11(HLH) (helix-loop-helix domain), AMPPNP, and double-stranded DNA. DNA binds between both coiled-coil domains of the Rad50 dimer with main interactions to a strand-loop-helix motif on the NBD. Our analysis suggests that this motif on Rad50 does not directly recognize DNA ends and binds internal sites on DNA. Functional studies reveal that DNA binding to Rad50 is not critical for DNA double-strand break repair but is important for telomere maintenance. In summary, we provide a structural framework for DNA binding to Rad50 in the ATP-bound state. Structure of the Rad50 DNA double-strand break repair protein in complex with DNA.,Rojowska A, Lammens K, Seifert FU, Direnberger C, Feldmann H, Hopfner KP EMBO J. 2014 Dec 1;33(23):2847-59. doi: 10.15252/embj.201488889. Epub 2014 Oct, 27. PMID:25349191[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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