title: Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.
abstract: Bloom'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.
authors.affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Newman
authors.affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Pavel
authors.initials: P
authors.lastname: Savitsky
authors.affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Allerston
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Building 18.1, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Anna H
authors.initials: AH
authors.lastname: Bizard
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Building 18.1, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Özgün
authors.initials: Ö
authors.lastname: Özer
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Building 18.1, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Kata
authors.initials: K
authors.lastname: Sarlós
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Building 18.1, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 , 1050 Brussels, Belgium Structural Biology Research Center, VIB, Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Pardon
authors.affiliation: Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2 , 1050 Brussels, Belgium Structural Biology Research Center, VIB, Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Steyaert
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Building 18.1, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hickson
authors.affiliation: Structural Genomics Consortium, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK opher.gileadi@sgc.ox.ac.uk.
authors.forename: Opher
authors.initials: O
authors.lastname: Gileadi
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061905:Single-Domain Antibodies / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D061905:Single-Domain Antibodies; D000244:Adenosine Diphosphate; D004247:DNA; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D015032:Zinc