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An evolutionarily conserved N-terminal leucine is essential for MX1 GTPase antiviral activity against different families of RNA viruses.
McKellar, Joe; Arnaud-Arnould, Mary; Chaloin, Laurent; Tauziet, Marine; Arpin-André, Charlotte; Pourcelot, Oriane; Blaise, Mickaël; Moncorgé, Olivier; Goujon, Caroline.
Afiliación
  • McKellar J; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Arnaud-Arnould M; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Chaloin L; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Tauziet M; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Arpin-André C; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Pourcelot O; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Blaise M; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Moncorgé O; IRIM, CNRS, Montpellier University, Montpellier, France. Electronic address: olivier.moncorge@irim.cnrs.fr.
  • Goujon C; IRIM, CNRS, Montpellier University, Montpellier, France. Electronic address: caroline.goujon@irim.cnrs.fr.
J Biol Chem ; 299(1): 102747, 2023 01.
Article en En | MEDLINE | ID: mdl-36436557
Myxovirus resistance protein 1 (MX1) and MX2 are homologous, dynamin-like large GTPases, induced upon interferon exposure. Human MX1 (HsMX1) is known to inhibit many viruses, including influenza A virus, by likely acting at various steps of their life cycles. Despite decades of studies, the mechanism(s) of action with which MX1 proteins manage to inhibit target viruses is not fully understood. MX1 proteins are mechano-enzymes and share a similar organization to dynamin, with a GTPase domain and a carboxy-terminal stalk domain, connected by a bundle signaling element. These three elements are known to be essential for antiviral activity. HsMX1 has two unstructured regions, the L4 loop, also essential for antiviral activity, and a short amino (N)-terminal region, which greatly varies between MX1 proteins of different species. The role of this N-terminal domain in antiviral activity is not known. Herein, using mutagenesis, imaging, and biochemical approaches, we demonstrate that the N-terminal domain of HsMX1 is essential for antiviral activity against influenza A virus, Vesicular Stomatitis Virus, and La Crosse virus. Furthermore, we pinpoint a highly conserved leucine within this region, which is absolutely crucial for human, mouse, and bat MX1 protein antiviral activity. Importantly, mutation of this leucine does not compromise GTPase activity or oligomerization capabilities but does modify MX1 protein subcellular localization. The discovery of this essential and highly conserved residue defines this region as key for antiviral activity and may reveal insights as to the mechanism(s) of action of MX1 proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Influenza A / Virus ARN / Proteínas de Resistencia a Mixovirus Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Influenza A / Virus ARN / Proteínas de Resistencia a Mixovirus Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos