comparative structural analysis of human dead-box rna helicases比较人类出局区rna解旋酶的结构分析.pdfVIP

Comparative Structural Analysis of Human DEAD-Box RNA Helicases ¨ 1 1 1 1 ¨ 1¤a Patrick Schutz , Tobias Karlberg , Susanne van den Berg , Ruairi Collins , Lari Lehtio , Martin ¨ 1¤b 1¤c 2 2 ¨ 1 Hogbom , Lovisa Holmberg-Schiavone , Wolfram Tempel , Hee-Won Park , Martin Hammarstrom , 1 1 ¨ 1 Martin Moche , Ann-Gerd Thorsell , Herwig Schu ler * 1 Structural Genomics Consortium, Karolinska Institutet, Stockholm, Sweden, 2 Structural Genomics Consortium and Department of Pharmacology, University of Toronto, Toronto, Canada Abstract 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 co