a motif unique to the human dead-box protein ddx3 is important for nucleic acid binding, atp hydrolysis, rnadna unwinding and hiv-1 replication主题独特的人类出局区蛋白质ddx3对核酸绑定很重要,atp水解,rnadna解除和hiv - 1复制.pdfVIP

A Motif Unique to the Human Dead-Box Protein DDX3 Is Important for Nucleic Acid Binding, ATP Hydrolysis, RNA/DNA Unwinding and HIV-1 Replication 1. 2. 1 2 1 Anna Garbelli , Sandra Beermann , Giulia Di Cicco , Ursula Dietrich , Giovanni Maga * 1 Institute of Molecular Genetics, National Research Council, Pavia, Italy, 2 Georg-Speyer-Haus Institute of Biomedical Research, Frankfurt, Germany Abstract DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication. Citation: Garbelli A, Beermann S, Di Cicco G, Dietrich U, Maga G (2011) A Motif Unique to the Human Dead-Box Protein DDX3 Is Important for Nucleic Acid