Regulation of measles virus gene expression by P protein coiled-coil properties
Science Advances 08 May 2019. Vol. 5, no. 5,
Louis-Marie Bloyet1, Antoine Schramm2, Carine Lazert, Bertrand Raynal, Maggy Hologne, Olivier Walker, Sonia Longhi2 and Denis Gerlier1,
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The polymerase of negative-stranded RNA viruses consists of the large protein (L) and the phosphoprotein (P), the latter serving both as a chaperon and a cofactor for L. We mapped within measles virus (MeV) P the regions responsible for binding and stabilizing L and showed that the coiled-coil multimerization domain (MD) of P is required for gene expression. MeV MD is kinked as a result of the presence of a stammer. Both restoration of the heptad regularity and displacement of the stammer strongly decrease or abrogate activity in a minigenome assay. By contrast, P activity is rather tolerant of substitutions within the stammer. Single substitutions at the “a” or “d” hydrophobic anchor positions with residues of variable hydrophobicity revealed that P functionality requires a narrow range of cohesiveness of its MD. Results collectively indicate that, beyond merely ensuring P oligomerization, the MD finely tunes viral gene expression through its cohesiveness.
Louis-Marie Bloyet1,*,†, Antoine Schramm2,*, Carine Lazert1, Bertrand Raynal3, Maggy Hologne4, Olivier Walker4, Sonia Longhi2,*,‡ and Denis Gerlier1,*,‡
1CIRI, International Center for Infectiology Research, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France.
2Aix-Marseille University, CNRS, Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257, Marseille, France.
3Institut Pasteur, Plateforme de Biophysique Moléculaire, Paris, France.
4Institut des Sciences Analytiques (ISA), Univ Lyon, CNRS, UMR5280, Université Claude Bernard Lyon 1, Lyon France.
↵‡Corresponding author. Email: sonia.longhI@afmb.univ-mrs.fr (S.L.); email@example.com (D.G.)
↵* These authors contributed equally to this work.