title: Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity.
abstract: The human myxovirus resistance protein 1 (MxA) is a key mediator of the interferon-induced antiviral response against a wide range of viruses. MxA expression is tightly regulated by type I and type III interferons, requires signal transducer and activator of transcription 1 signaling, and is not inducible directly by viruses or other stimuli. MxA shares many properties with the dynamin superfamily of large GTPases. It consists of 3 domains, namely, an N-terminal GTPase domain that binds and hydrolyses GTP, a middle domain mediating self-assembly, and a carboxy-terminal GTPase effector domain. Like dynamin, MxA has the ability to self-assemble into highly ordered oligomers and to form ring-like structures around liposomes, inducing liposome tubulation. The structural details of MxA oligomerization have recently been elucidated, providing new insights into the antiviral mechanism of this mechanochemical enzyme. The structural and functional data suggest that MxA targets the nucleoprotein of MxA-sensitive viruses. Thus, MxA may form oligomeric rings around tubular nucleocapsid structures, thereby inhibiting their transcriptional and replicative function. Here we briefly review the most salient features of MxA expression and antiviral function.
authors.affiliation: Department of Virology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany. otto.haller@uniklinik-freiburg.de
authors.forename: Otto
authors.initials: O
authors.lastname: Haller
authors.forename: Georg
authors.initials: G
authors.lastname: Kochs
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D012328:RNA Viruses / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism
chemical_list: C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019590:Nucleocapsid Proteins; D050794:STAT1 Transcription Factor; D007372:Interferons; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins