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
Related in: MedlinePlus
Mentions: The individual fold of the two RecA domains is very similar to the HsRECQ1 and E. coli RecQ (EcRecQ) structures (22,54), with RMSD's between equivalent Cα atoms of 1.5 Å. However, the relative positioning of these two domains differs significantly in all three structures, with the BLM and HsRECQ1 being the most different and EcRecQ being somewhat intermediate (Figure 2A). The inter-domain movement can be described as a rigid body shift of up to 20°, with the loop connecting the two domains (residues 855–858) acting as a hinge, resulting in maximal displacements of equivalent regions of up to 15 Å. The cleft between the two RecA domains is considerably narrower in BLM than in either EcRecQ or HsRECQ1, with the D1-D2 conformation in BLM crystals appearing to be quite distinct amongst the SF2 family helicase structures solved to date.
Affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.