Dynamin-like MxA GTPase: structural insights into oligomerization and implications for antiviral activity.
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.
Haller
Otto
O
Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany. otto.haller@uniklinik-freiburg.de
Gao
Song
S
von der Malsburg
Alexander
A
Daumke
Oliver
O
Kochs
Georg
G
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D034281:Dynamins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D009980:Influenza A virus / Q000378:metabolism; D007251:Influenza, Human / Q000188:drug therapy / Q000201:enzymology; D064547:Myxovirus Resistance Proteins; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins; D034281:Dynamins