Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.
Bottom Line: 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.
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.