Dynamin-like MxA GTPase: structural insights into oligomerization and implications for antiviral activity

J Biol Chem. 2010 Sep 10;285(37):28419-24. doi: 10.1074/jbc.R110.145839. Epub 2010 Jun 10.

Abstract

The interferon-inducible MxA GTPase is a key mediator of cell-autonomous innate immunity against a broad range of viruses such as influenza and bunyaviruses. MxA shares a similar domain structure with the dynamin superfamily of mechanochemical enzymes, including an N-terminal GTPase domain, a central middle domain, and a C-terminal GTPase effector domain. Recently, crystal structures of a GTPase domain dimer of dynamin 1 and of the oligomerized stalk of MxA (built by the middle and GTPase effector domains) were determined. These data provide exciting insights into the architecture and antiviral function of the MxA oligomer. Moreover, the structural knowledge paves the way for the development of novel antiviral drugs against influenza and other highly pathogenic viruses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use
  • Crystallography, X-Ray
  • Dynamins / chemistry*
  • Dynamins / immunology
  • Dynamins / metabolism
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / immunology
  • GTP-Binding Proteins / metabolism
  • Humans
  • Immunity, Innate / physiology
  • Influenza A virus / metabolism
  • Influenza, Human / drug therapy
  • Influenza, Human / enzymology
  • Myxovirus Resistance Proteins
  • Protein Multimerization*
  • Protein Structure, Tertiary
  • Structural Homology, Protein
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • GTP-Binding Proteins
  • Dynamins