Role of GTPase activity of murine Mx1 protein in nuclear localization and anti-influenza virus activity.
Murine Mx1 protein is an interferon-inducible GTPase which localizes in nuclei and inhibits influenza virus infection. Wild-type Mx1 and two mutant Mx1 proteins, each carrying a single mutation either in the GTP-binding motif (S50I) or in the self-assembly motif (C71S), were expressed in MDCK cells. Wild-type Mx1 localized in nuclei, forming small granules with minute dots, and inhibited influenza virus growth. Mutant S50I, which had no GTP-binding or GTPase activities, formed linear structures in nuclei and lacked anti-viral activity, while C71S appeared diffuse in nuclei as minute dots without granules, but retained the inhibitory activity against influenza virus growth. A correlation existed between GTPase activity, intranuclear distribution and antiviral activity. We concluded that GTPase activity is essential for expression of the biological activity of Mx1 protein.
Toyoda
T
T
Department of Molecular Genetics, National Institute of Genetics, Mishima, Shizuoka, Japan.
Asano
Y
Y
Ishihama
A
A
D000818:Animals; D000998:Antiviral Agents / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics* / Q000821:virology; D004285:Dogs; D020558:GTP Phosphohydrolases / Q000502:physiology*; D019204:GTP-Binding Proteins; D005822:Genetic Vectors; D009980:Influenza A virus / Q000201:enzymology / Q000254:growth & development*; D051379:Mice; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins