title: A stabilized headless measles virus attachment protein stalk efficiently triggers membrane fusion.
abstract: Paramyxovirus attachment and fusion (F) envelope glycoprotein complexes mediate membrane fusion required for viral entry. The measles virus (MeV) attachment (H) protein stalk domain is thought to directly engage F for fusion promotion. However, past attempts to generate truncated, fusion-triggering-competent H-stem constructs remained fruitless. In this study, we addressed the problem by testing the hypothesis that truncated MeV H stalks may require stabilizing oligomerization tags to maintain intracellular transport competence and F-triggering activity. We engineered H-stems of different lengths with added 4-helix bundle tetramerization domains and demonstrate restored cell surface expression, efficient interaction with F, and fusion promotion activity of these constructs. The stability of the 4-helix bundle tags and the relative orientations of the helical wheels of H-stems and oligomerization tags govern the kinetics of fusion promotion, revealing a balance between H stalk conformational stability and F-triggering activity. Recombinant MeV particles expressing a bioactive H-stem construct in the place of full-length H are viable, albeit severely growth impaired. Overall, we demonstrate that the MeV H stalk represents the effector domain for MeV F triggering. Fusion promotion appears linked to the conformational flexibility of the stalk, which must be tightly regulated in viral particles to ensure efficient virus entry. While the pathways toward assembly of functional fusion complexes may differ among diverse members of the paramyxovirus family, central elements of the triggering machinery emerge as highly conserved.
authors: Center for Inflammation, Immunity & Infection, Georgia State University, Atlanta, Georgia, USA.
authors: Melinda A
authors: MA
authors: Brindley
authors: Rolf
authors: R
authors: Suter
authors: Isabel
authors: I
authors: Schestak
authors: Gabriella
authors: G
authors: Kiss
authors: Elizabeth R
authors: ER
authors: Wright
authors: Richard K
authors: RK
authors: Plemper
mesh_terms: D000818:Animals; D002460:Cell Line; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017384:Sequence Deletion; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D014760:Viral Fusion Proteins; D014764:Viral Proteins
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