a transient homotypic interaction model for the influenza a virus ns1 protein effector domain瞬态同型的交互模型的甲型流感病毒ns1蛋白效应域.pdfVIP

A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain 1 2 1 1 1¤ ´ Philip S. Kerry , Juan Ayllon , Margaret A. Taylor , Claudia Hass , Andrew Lewis , Adolfo Garcıa- Sastre2,3,4, Richard E. Randall 1, Benjamin G. Hale2*, Rupert J. Russell 1* 1 Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, United Kingdom, 2 Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America, 3 Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America, 4 Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York, United States of America Abstract Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal ‘tail’. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization