title: A residue located at the junction of the head and stalk regions of measles virus fusion protein regulates membrane fusion by controlling conformational stability.
abstract: The fusion (F) protein of measles virus performs refolding from the thermodynamically metastable prefusion form to the highly stable postfusion form via an activated unstable intermediate stage, to induce membrane fusion. Some amino acids involved in the fusion regulation cluster in the heptad repeat B (HR-B) domain of the stalk region, among which substitution of residue 465 by various amino acids revealed that fusion activity correlates well with its side chain length from the Cα (P<0.01) and van der Waals volume (P<0.001), except for Phe, Tyr, Trp, Pro and His carrying ring structures. Directed towards the head region, longer side chains of the non-ring-type 465 residues penetrate more deeply into the head region and may disturb the hydrophobic interaction between the stalk and head regions and cause destabilization of the molecule by lowering the energy barrier for refolding, which conferred the F protein enhanced fusion activity. Contrarily, the side chain of ring-type 465 residues turned away from the head region, resulting in not only no contact with the head region but also extensive coverage of the HR-B surface, which may prevent the dissociation of the HR-B bundle for initiation of membrane fusion and suppress fusion activity. Located in the HR-B domain just at the junction between the head and stalk regions, amino acid 465 is endowed with a possible ability to either destabilize or stabilize the F protein depending on its molecular volume and the direction of the side chain, regulating fusion activity of measles virus F protein.
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Satoh
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Saeka
authors.initials: S
authors.lastname: Yonemori
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shogaki
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, 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, Seta Tsukinowa-cho, 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, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Gotoh
authors.affiliation: Department of Computer Bioscience, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Department of Computer Bioscience, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Takahashi
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D006801:Humans; D008457:Measles / Q000821:virology*; D008459:Measles virus / Q000737:chemistry* / Q000648:ultrastructure; D008561:Membrane Fusion; D000072417:Protein Domains; D017510:Protein Folding; D055550:Protein Stability; D013816:Thermodynamics; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry*
chemical_list: D014760:Viral Fusion Proteins