Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper Journal Article


Authors: Melén, K.; Ronni, T.; Broni, B.; Krug, R. M.; von Bonsdorff, C. H.; Julkunen, I.
Article Title: Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper
Abstract: Interferons induce a number of different protein that mediate the antiproliferative, antiviral, and immunomodulatory functions of interferons. At least three different proteins mediate the antiviral response, and one of them, Mx protein, specifically inhibits the replication of influenza virus and (vesicular stomatitis virus). Mouse and rat Mx1 proteins are nuclear, whereas other presently known Mx proteins are cytoplasmic. The cellular functions of Mx proteins are unknown, but all of them contain a consensus GTP binding site. Very little information is available on the structure and characteristics of the mouse Mx1 protein itself. For biochemical characterization, we expressed mouse Mx1 protein in a baculovirus system and purified it to homogeneity. The purified protein as well as the authentic murine cellular Mx1 protein exists in dimers and trimers in the presence of dissociating solvents, whereas in physiological buffers they form aggregates. Cross-linking experiments done on Mx-expressing cells from various species revealed that mouse, rat, and human Mx proteins exist predominantly in trimers. Amino acid sequence analysis shows that all known Mx proteins have conserved leucine repeats typical for a leucine zipper at their COOH-terminal end. In vitro translation of chimeric catechol O-methyltransferase-Mx1 gene constructs revealed that the leucine zipper domain of Mx1 protein is responsible for the oligomerization. The COOH terminus also functions as a nuclear localization signal. Microinjection of purified oligomers into the cell cytoplasm resulted in a fast accumulation of the protein in the nucleus. Immunoelectron microscopy revealed that nuclear murine Mx1 protein exists in distinct, electron-dense structures separate from nuclear membrane, and chromatin, or nucleolus. These observations reveal that a COOH-terminal leucine zipper domain is an important structural element of all Mx proteins. Its relevance to the biology and functions of Mx proteins is presently not known.
Keywords: gene; transcription; resistance; expression; cells; molecular-cloning; binding proteins; influenza-virus; catechol-o-methyltransferase; heptad repeat region
Journal Title: Journal of Biological Chemistry
Volume: 267
Issue: 36
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 1992-12-25
Start Page: 25898
End Page: 25907
Language: English
ACCESSION: WOS:A1992KD07300048
PROVIDER: Clarivate Analytics Web of Science
PROVIDER: wos
PUBMED: 1281477
DOI: 10.1016/S0021-9258(18)35693-X
Notes: Article -- Source: Wos
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  1. Robert M. Krug
    18 Krug