Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.
Bottom Line: 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.
Affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.Show MeSH
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Mentions: During the late stages of preparation of this manuscript another study was published in which the authors describe a structure of BLM in complex with ADP and DNA (PDB: 4O3M; (67)). This structure, determined at 2.3-Å resolution obtained in the presence of a 16-bp DNA duplex with an 8-bp overhang, is very similar to our DNA complex, and can be aligned with a 1.5-Å RMSD over the entire structure (Figure 7A). Comparing the individual domains separately reveals an even higher degree of similarity, indicating a slight difference is present in their relative positioning (Figure 7B). Superposition on the basis of the D1 domain alone reveals a small difference in WH domain orientation (maximal displacements of ∼4.5 Å between equivalent residues), which is possibly a result of the different lengths of double-stranded DNA present.
Affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.