4cgz
Crystal structure of the Bloom's syndrome helicase BLM in complex with DNA
Structural highlights
DiseaseBLM_HUMAN Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionBLM_HUMAN Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).[1] [2] [3] [4] Publication Abstract from PubMedBloom's syndrome helicase (BLM) is a member of the RecQ family of DNA helicases, which play key roles in the maintenance of genome integrity in all organism groups. We describe crystal structures of the BLM helicase domain in complex with DNA and with an antibody fragment, as well as SAXS and domain association studies in solution. We show an unexpected nucleotide-dependent interaction of the core helicase domain with the conserved, poorly characterized HRDC domain. The BLM-DNA complex shows an unusual base-flipping mechanism with unique positioning of the DNA duplex relative to the helicase core domains. Comparison with other crystal structures of RecQ helicases permits the definition of structural transitions underlying ATP-driven helicase action, and the identification of a nucleotide-regulated tunnel that may play a role in interactions with complex DNA substrates. Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.,Newman JA, Savitsky P, Allerston CK, Bizard AH, Ozer O, Sarlos K, Liu Y, Pardon E, Steyaert J, Hickson ID, Gileadi O Nucleic Acids Res. 2015 Apr 21. pii: gkv373. PMID:25901030[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
