A functional GTP-binding motif is necessary for antiviral activity of Mx proteins.
AUTOR(ES)
Pitossi, F
RESUMO
Mx proteins are interferon-induced GTPases that inhibit the multiplication of certain negative-stranded RNA viruses. However, it has been unclear whether GTPase activity is necessary for antiviral function. Here, we have introduced mutations into the tripartite GTP-binding consensus elements of the human MxA and mouse Mx1 proteins. The invariant lysine residue of the first consensus motif, which interacts with the beta- and gamma-phosphates of bound GTP in other GTPases, was deleted or replaced by methionine or alanine. These Mx mutants and appropriate controls were then tested for antiviral activity, GTP-binding capacity, and GTPase activity. We found a direct correlation between the GTP-binding capacities and GTP hydrolysis activities of the purified Mx mutants in vitro and their antiviral activities in transfected 3T3 cells, demonstrating that a functional GTP-binding motif is necessary for virus inhibition. Our results, thus, firmly establish antiviral activity as a novel function of a GTPase, emphasizing the enormous functional diversity of GTPase superfamily members.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=238112Documentos Relacionados
- Structural and functional similarities between the nucleotide-binding domains of CFTR and GTP-binding proteins.
- Similarity of nucleotide interactions of BiP and GTP-binding proteins.
- Antagonists with negative intrinsic activity at delta opioid receptors coupled to GTP-binding proteins.
- A GTP-binding protein of Escherichia coli has homology to yeast RAS proteins.
- Microsomal and cytosolic fractions of guinea pig hepatocytes contain 100-kilodalton GTP-binding proteins reactive with antisera against alpha subunits of stimulatory and inhibitory heterotrimeric GTP-binding proteins.
