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

TitleCrystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.
Publication TypeJournal Article
Year of Publication2015
AuthorsNewman, J. A., P. Savitsky, C. K. Allerston, A. H. Bizard, Ö. Özer, K. Sarlós, Y. Liu, E. Pardon, J. Steyaert, I. D. Hickson, and O. Gileadi
JournalNucleic Acids Res
Volume43
Issue10
Pagination5221-35
Date Published2015 May 26
ISSN1362-4962
KeywordsAdenosine Diphosphate, Crystallography, X-Ray, DNA, Models, Molecular, Mutation, Protein Conformation, Protein Structure, Tertiary, RecQ Helicases, Single-Domain Antibodies, Zinc
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.

DOI10.1093/nar/gkv373
Alternate JournalNucleic Acids Res.
PubMed ID25901030
PubMed Central IDPMC4446433
Grant List092809/Z/10/Z / / Wellcome Trust / United Kingdom
Research group: