Comparative structural analysis of human DEAD-box RNA helicases.

• Main Authors: Patrick Schütz, Tobias Karlberg, Susanne van den Berg, Ruairi Collins, Lari Lehtiö, Martin Högbom, Lovisa Holmberg-Schiavone, Wolfram Tempel, Hee-Won Park, Martin Hammarström, Martin Moche, Ann-Gerd Thorsell, Herwig Schüler
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-09-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2948006?pdf=render

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members.