title: Intramolecular complementation of measles virus fusion protein stability confers cell-cell fusion activity at 37 °C.
abstract: The fusion (F) protein of measles virus mediates membrane fusion. In this study, we investigated the molecular basis of the cell-cell fusion activity of the F protein. The N465H substitution in the heptad repeat B domain of the stalk region of the F protein eliminates this activity, but an additional mutation in the DIII domain of the head region - N183D, F217L, P219S, I225T or G240R - restores cell-cell fusion. Thermodynamically stabilized by the N465H substitution, the F protein required elevated temperature as high as 40 °C to promote cell-cell fusion, whereas all five DIII mutations caused destabilization of the F protein allowing the highest fusion activity at 30 °C. Stability complementation between the two domains conferred an efficient cell-cell fusion activity on the F protein at 37 °C.
authors.affiliation: Division of Microbiology, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Satoh
authors.affiliation: Division of Microbiology, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Division of Microbiology, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shogaki
authors.affiliation: Division of Microbiology, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakimoto
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Gotoh
authors.affiliation: Division of Biophysics, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Microbiology, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan. Electronic address: m_itoh@nagahama-i-bio.ac.jp.
authors.forename: Masae
authors.initials: M
authors.lastname: Itoh
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D008459:Measles virus / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014760:Viral Fusion Proteins
keywords: Fusion protein; Measles virus; Membrane fusion; Refolding; Thermodynamic stability