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. 1993 Nov;67(11):6726–6732. doi: 10.1128/jvi.67.11.6726-6732.1993

A functional GTP-binding motif is necessary for antiviral activity of Mx proteins.

F Pitossi 1, A Blank 1, A Schröder 1, A Schwarz 1, P Hüssi 1, M Schwemmle 1, J Pavlovic 1, P Staeheli 1
PMCID: PMC238112  PMID: 8411374

Abstract

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.

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Selected References

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