Human MxB protein, an interferon-alpha-inducible GTPase, contains a nuclear targeting signal and is localized in the heterochromatin region beneath the nuclear envelope.
Interferon-inducible Mx proteins belong to the family of large GTPases and are highly homologous with dynamins within their GTP-binding domain. Cytoplasmically localized human MxA protein mediates resistance to influenza and several other viruses, whereas human MxB protein has not been found to have any antiviral activity. Here we show that MxB protein is found both in the cytoplasm and in the nucleus, where it is localized in a granular pattern in the heterochromatin region beneath the nuclear envelope. Transfection experiments in COS cells of N-terminally deleted MxB constructs revealed a functional nuclear localization signal within the first 24 N-terminal amino acids. Nuclear 78-kDa and cytoplasmic 76-kDa forms of MxB protein were found in all of the cell lines studied and in human peripheral blood mononuclear cells. MxB protein proved to be a functional GTPase with activity comparable to that of MxA protein. N-terminally truncated (delta1-82) MxB protein lacking both the nuclear localization signal and a proline-rich domain had almost completely lost its GTPase activity. Analysis of peripheral blood mononuclear cells suggested that MxB protein expression is strictly regulated by interferon-alpha. This is the first documentation that human Mx protein resides in the nucleus. It also emphasizes that there are considerable differences in the localization and structure of functional domains within Mx proteins.
Melén
K
K
Department of Virology, National Public Health Institute, FIN-00300 Helsinki, Finland.
Keskinen
P
P
Ronni
T
T
Sareneva
T
T
Lounatmaa
K
K
Julkunen
I
I
D000595:Amino Acid Sequence; D001692:Biological Transport; D002451:Cell Compartmentation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D004252:DNA Mutational Analysis; D019084:Fluorescent Antibody Technique, Indirect; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D019204:GTP-Binding Proteins; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000737:chemistry*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry; D016253:Microscopy, Immunoelectron; D008957:Models, Genetic; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D017384:Sequence Deletion
D016207:Cytokines; D006570:Heterochromatin; C579071:MX1 protein, human; C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; D011506:Proteins; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins